Aldosterone Synthase: A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.Aldosterone: A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.Steroid 11-beta-Hydroxylase: A mitochondrial cytochrome P450 enzyme that catalyzes the 11-beta-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11B1 gene, is important in the synthesis of CORTICOSTERONE and HYDROCORTISONE. Defects in CYP11B1 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Fadrozole: A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.Hypoaldosteronism: A congenital or acquired condition of insufficient production of ALDOSTERONE by the ADRENAL CORTEX leading to diminished aldosterone-mediated synthesis of Na(+)-K(+)-EXCHANGING ATPASE in renal tubular cells. Clinical symptoms include HYPERKALEMIA, sodium-wasting, HYPOTENSION, and sometimes metabolic ACIDOSIS.Hyperaldosteronism: A condition caused by the overproduction of ALDOSTERONE. It is characterized by sodium retention and potassium excretion with resultant HYPERTENSION and HYPOKALEMIA.18-Hydroxycorticosterone: 11 beta,18,21-Trihydroxypregn-4-ene-3,20-dione.Receptors, Mineralocorticoid: Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.Mineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)Adrenal Glands: A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.Adrenal Cortex: The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.Mineralocorticoids: A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.Zona Glomerulosa: The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert PREGNENOLONE to ALDOSTERONE. The final steps involve three successive oxidations by CYTOCHROME P-450 CYP11B2.Renin-Angiotensin System: A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.Renin: A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Corticosterone: An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)Nuclear Receptor Subfamily 4, Group A, Member 2: An orphan nuclear receptor that is found at high levels in BRAIN tissue. The protein is believed to play a role in development and maintenance of NEURONS, particularly dopaminergic neurons.Angiotensinogen: An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Citrate (si)-Synthase: Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cholestanetriol 26-Monooxygenase: An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.Indenes: A family of fused-ring hydrocarbons isolated from coal tar that act as intermediates in various chemical reactions and are used in the production of coumarone-indene resins.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Alkynes: Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Animal DiseasesProstatic Neoplasms: Tumors or cancer of the PROSTATE.Meta-Analysis as Topic: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Access to Information: Individual's rights to obtain and use information collected or generated by others.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Peer Review, Research: The evaluation by experts of the quality and pertinence of research or research proposals of other experts in the same field. Peer review is used by editors in deciding which submissions warrant publication, by granting agencies to determine which proposals should be funded, and by academic institutions in tenure decisions.Hyperkalemia: Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)Hypokalemia: Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity.Potassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.Whole-Body Counting: Measurement of radioactivity in the entire human body.
Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. (1/218)
Significant correlation of body sodium and potassium with blood pressure (BP) may suggest a role for aldosterone in essential hypertension. In patients with this disease, the ratio of plasma renin to plasma aldosterone may be lower than in control subjects and plasma aldosterone levels may be more sensitive to angiotensin II (Ang II) infusion. Because essential hypertension is partly genetic, it is possible that altered control of aldosterone synthase gene expression or translation may be responsible. We compared the frequency of 2 linked polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (IC), in groups of hypertensive and normotensive subjects. In a larger population, the relationship of aldosterone excretion rate to these polymorphisms was also evaluated. In 138 hypertensive subjects, there was a highly significant excess of TT homozygosity (SF-1) over CC homozygosity compared with a group of individually matched normotensive control subjects. The T allele was significantly more frequent than the C allele in the hypertensive group compared with the control group. Similarly, there was a highly significant relative excess of the conversion allele over the "wild-type" allele and of conversion homozygosity over wild-type homozygosity in the hypertensive group compared with the control group. In 486 subjects sampled from the North Glasgow Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population, SF-1 and IC genotypes were compared with tetrahydroaldosterone excretion rate. Subjects with the SF-1 genotypes TT or TC had significantly higher excretion rates than those with the CC genotype. The T allele was associated with higher excretion rates than the C allele. However, no significant differences were found in excretion rate between subjects of different IC genotype. Urinary aldosterone excretion rate may be a useful intermediate phenotype linking these genotypes to raised BP. However, no causal relationship has yet been established, and it is possible that the polymorphisms may be in linkage with other causative mutations. (+info)Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. (2/218)
BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples. (+info)Changes in the glomerulosa cell phenotype during adrenal regeneration in rats. (3/218)
In situ hybridization was used to examine cellular differentiation during rat adrenal regeneration, defining zona glomerulosa [cytochrome P-450 aldosterone synthase (P-450aldo) mRNA positive], zona fasciculata [cytochrome P-450 11beta-hydroxylase (P-45011beta) mRNA positive], or zona intermedia [negative for both but 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA positive]. After unilateral adrenal enucleation with contralateral adrenalectomy (ULE/ULA), the expression of all mRNA was reduced at 2 days. From 5 to 10 days, P-45011beta and 3beta-HSD mRNA increased while P-450aldo remained low; at 20 days, all mRNA were increased. From 2 to 10 days, cells adjacent to the capsule showed intermedia cell differentiation; by 20 days, the subcapsular glomerulosa cells reappeared. This suggests that after enucleation the glomerulosa dedifferentiates to zona intermedia. The experiment was repeated in rats where the postenucleation ACTH rise was prevented. Rats underwent ULE with sham ULA (ULE/SULA) or ULE/SULA with ACTH treatment. Adrenals from ULE/SULA rats expressed increased P-450aldo mRNA at 10 days and reduced P-45011beta mRNA and adrenal weight at 30 days. ACTH treatment reversed the pattern toward that seen in ULE/ULA. These findings show that the enucleation-induced dedifferentitation of the glomerulosa cell may result in part from elevated plasma ACTH and that prevention of dedifferentiation may result in impaired regeneration. (+info)Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. (4/218)
The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets. (+info)Modulation of aldosterone biosynthesis by adrenodoxin mutants with different electron transport efficiencies. (5/218)
Aldosterone biosynthesis is highly regulated on different levels by hormones, potassium, lipid composition of the membrane and the molecular structure of its gene. Here, the influence of the electron transport efficiency from adrenodoxin (Adx) to CYP11B1 on the activities of bovine CYP11B1 has been investigated using a liposomal reconstitution system with truncated mutants of Adx. It could be clearly demonstrated that Adx mutants Adx 4-114 and Adx 4-108, possessing enhanced electron transfer abilities, produce increases in corticosterone and aldosterone biosynthesis. Based on the Vmax values of corticosterone and aldosterone formation, Adx 4-108 and Adx 4-114 enhance corticosterone synthesis 1.3-fold and aldosterone formation threefold and twofold, respectively. The production of 18-hydroxycorticosterone was changed only slightly in these Adx mutants. The effect of Adx 1-108 on the product patterns of bovine CYP11B1, human CYP11B1 and human CYP11B2 was confirmed in COS-1 cells by cotransfection of CYP11B- and Adx-containing expression vectors. It could be shown that Adx 1-108 enhances the formation of aldosterone by bovine CYP11B1 and by human CYP11B2, and stimulates the production of corticosterone by bovine CYP11B1 and human CYP11B1 and CYP11B2 also. (+info)Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction. (6/218)
BACKGROUND: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI. METHODS AND RESULTS: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the -344C allele. However, this allele was associated in a gene dosage-dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same genotype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. CONCLUSIONS: Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the -344C allele of CYP11B2. (+info)Baroreflex sensitivity and variants of the renin angiotensin system genes. (7/218)
OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS. (+info)Ontogeny of angiotensin II type 1 receptor and cytochrome P450(c11) in the sheep adrenal gland. (8/218)
In the present study we investigated the ontogeny of the expression of the type 1 angiotensin receptor (AT(1)R mRNA) and the zonal localization of AT(1)R immunoreactivity (AT(1)R-ir) and cytochrome P450(c11) (CYP11B-ir) in the sheep adrenal gland. In the adult sheep and in the fetus from as early as 90 days gestation, intense AT(1)R-ir was observed predominantly in the zona glomerulosa and to a lesser extent in the zona fasciculata, and it was not detectable in the adrenal medulla. AT(1)R mRNA decreased 4-fold between 105 days and 120 days, whereas AT(1)R mRNA levels remained relatively constant between 120 days and the newborn period. In contrast, both in the adult sheep and in the fetal sheep from as early as 90 days gestation, intense CYP11B-ir was consistently detected throughout the adrenal cortex and in steroidogenic cells that surround the central adrenal vein. In conclusion, we speculate that the presence of AT(1)R in the zona fasciculata, and the higher levels of expression of AT(1)R at around 100 days gestation, may suggest that suppression of CYP17 is mediated via AT(1)R at this time. The abundant expression of AT(1)R-ir and CYP11B-ir in the zona glomerulosa of the fetal sheep adrenal gland would also suggest that lack of angiotensin II stimulation of aldosterone secretion is not due to an absence of AT(1)R or CYP11B in the zona glomerulosa. (+info)2002). "Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase". Endocrinology. 143 (9): 3651- ... Komeima K, Hayashi Y, Naito Y, Watanabe Y (2000). "Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin- ... 1999). "Regulation of neuronal nitric-oxide synthase by calmodulin kinases". J. Biol. Chem. 274 (29): 20597-602. doi:10.1074/ ... "Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/ ...
Hampf M, Dao NT, Hoan NT, Bernhardt R (September 2001). "Unequal crossing-over between aldosterone synthase and 11beta- ... "Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase". J. Clin ... "Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase". Nat Genet. 2 (1 ...
... is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. ... Steroidogenesis Deoxycorticosterone Aldosterone 11-Deoxycortisol 11-Deoxycorticosterone Cortisol R.A. Hill; H.L.J. Makin; D.N. ... Corticosterone is the precursor molecule to the mineralocorticoid aldosterone, one of the major homeostatic modulators of ... potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. ...
The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. ... too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which ... produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more salt than normal, which in ... The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone ...
... by the action of the enzyme aldosterone synthase. Aldosterone plays an important role in the long-term regulation of blood ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem ... In the kidneys, aldosterone acts on the distal convoluted tubules and the collecting ducts by increasing the reabsorption of ... Aldosterone is responsible for the reabsorption of about 2% of filtered glomerular filtration rates. Sodium retention is also a ...
The enzyme aldosterone synthase (also known as CYP11B2) acts in this location The expression of neuron-specific proteins in the ... Zhou, M.Y.; Gomez-Sanchez, C.E. (1993). "Cloning and Expression of a Rat Cytochrome P-450 11β-Hydroxylase/Aldosterone Synthase ... the 2 major regulators of aldosterone production. Aldosterone regulates the body's concentration of electrolytes, primarily ... Ye, P.; Mariniello, B.; Mantero, F.; Shibata, H.; Rainey, W. E (2007). "G-protein-coupled receptors in aldosterone-producing ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... and aldosterone (C 21H 28O 5). (Note that aldosterone and cortisone share the same chemical formula but the structures are ... Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ...
It serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the zona glomerulosa:. ...
"Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, ... molecular dynamics simulation studies also indicate that ethyl caffeate is a potential inhibitor of the aldosterone synthase ( ... CYP11B2), a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure ...
It specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β- ...
Hyperaldosteronism Pseudohyperaldosteronism Glucocorticoid-remediable aldosteronism Aldosterone and aldosterone synthase Maria ... In serum both aldosterone and renin levels are low[citation needed] This disorder presents similarly to hyperaldosteronism, ... The treatment for AME is based on the blood pressure control with Aldosterone antagonist like Spironalactone which also ... The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the ...
Aldosterone synthase (CYP11B2) inhibitors such as metyrapone, mitotane, and osilodrostat prevent the production of the potent ... Farnesyl pyrophosphate synthase (FPPS) inhibitors prevent the conversion of isopentenyl pyrophosphate (IPP) into farnesyl ... Jürg Müller (6 December 2012). Regulation of Aldosterone Biosynthesis. Springer Science & Business Media. pp. 39-. ISBN 978-3- ... and aldosterone from the less potent corticosteroids 11-deoxycorticosterone and 11-deoxycortisol and are used in the diagnosis ...
Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase ... The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Control of aldosterone ... Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone. It is ...
Corticosterone is then converted to aldosterone by aldosterone synthase. Most of the DOC is secreted by the zona fasciculata of ... DOC has about 1/20 of the sodium retaining power of aldosterone, and is said to be as little as one per cent of aldosterone at ... DOC is a precursor molecule for the production of aldosterone. The major pathway for aldosterone production is in the adrenal ... Since DOC has about 1/5 the potassium excreting power of aldosterone, it probably must have aldosterone's help if the serum ...
... by the action of the enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely responsible for the long-term ... is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2). ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem. ... Aldosterone is largely responsible for the long-term regulation of blood pressure. Aldosterone effects on the distal convoluted ...
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol). The first ...
... aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent. In addition, mitotane has ...
... aldosterone synthase MeSH D12.776.422.220.453.915.099 - aromatase MeSH D12.776.422.220.453.915.200 - cholesterol 7 alpha- ... aldosterone MeSH D12.776.827.275.700.500 - tacrolimus binding protein 1a MeSH D12.776.828.075.350.275 - filgrastim MeSH D12.776 ...
... the Gene mutated will result in an aldosterone synthase that is ACTH-sensitive, which is normally not. GRA appears to be the ... Compare these effects to those seen in Conn's disease, an adrenocortical tumor which causes excess release of aldosterone, that ... Ziaja J, Cholewa K, Mazurek U, Cierpka L (2008). "[Molecular basics of aldosterone and cortisol synthesis in normal adrenals ... DOC has blood-pressure raising effects similar to aldosterone, and abnormally high levels result in hypokalemic hypertension. ...
... aldosterone synthase) - mineralocorticoid synthesis 21-Hydroxylase - corticosteroid synthesis Cytochrome P450 (CYP1, 2, 3) - ...
... aldosterone synthase MeSH D08.244.453.915.099 --- aromatase MeSH D08.244.453.915.200 --- cholesterol 7 alpha-hydroxylase MeSH ... riboflavin synthase MeSH D08.811.913.225.825 --- spermidine synthase MeSH D08.811.913.225.912 --- spermine synthase MeSH ... aldosterone synthase MeSH D08.811.682.690.708.170.915.099 --- aromatase MeSH D08.811.682.690.708.170.915.200 --- cholesterol 7 ... aldosterone synthase MeSH D08.811.682.690.708.783.099 --- aromatase MeSH D08.811.682.690.708.783.200 --- cholesterol 7 alpha- ...
Aldosterone synthase deficiency Secondary Aldosterone deficiency Secondary adrenal insufficiency Diseases of the pituitary or ... Isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The two ... In medicine (endocrinology), hypoaldosteronism refers to decreased levels of the hormone aldosterone. ... Aldosterone deficiency should be treated with a mineralocorticoid (such as fludrocortisone), as well as possibly a ...
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol). Glutamate ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... Note: aldosterone synthase is absent in other sections of the adrenal gland. Aldosterone synthesis is stimulated by several ... The last parts are mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone ... It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Aldosterone is the ...
Aldosterone is synthesized by following the metabolism of progesterone. In the potential case where aldosterone synthase is not ... Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona ... Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone ... Aldosterone synthase is encoded on chromosome 8q22 by the CYP11B2 gene. The gene contains 9 exons and spans roughly 7000 base ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
Pharmacodynamic effects of aldosterone synthase inhibition: single-dose phase. Plasma and urinary aldosterone. Single doses of ... Pharmacodynamic effects of aldosterone synthase inhibition: multiple-dose phase. Plasma and urinary aldosterone. Compared with ... Selective inhibition of aldosterone synthase appears to be a promising approach to treat diseases associated with aldosterone ... In the first 12 h after dosing, LCI699 effectively inhibited the activity of aldosterone synthase and plasma aldosterone was ...
Background: Isolated hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency is a rare autosomal recessive ... disorder linked to aldosterone biosynthesis defect (involving CYP11B2 gene). Its clinical presentation varies with age: during ...
... leading to hypersecretion of adrenal androgens with reduced production of cortisol and aldosterone), or aldosterone synthase ... primary defects in adrenal synthesis or secretion of aldosterone, and aldosterone resistance. The major clinical manifestations ... 1) Primary aldosterone deficiency should be suspected in persons who have hyperkalemia despite normal renal function and lack ... 3) Aldosterone resistance: Type I and type II pseudohypoaldosteronism, potassium-sparing diuretics that compete for the ...
Aldosterone is synthesized by following the metabolism of progesterone. In the potential case where aldosterone synthase is not ... Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona ... Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone ... Aldosterone synthase is encoded on chromosome 8q22 by the CYP11B2 gene. The gene contains 9 exons and spans roughly 7000 base ...
Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing ... aldosterone after ADX and reduction of aldosterone due to pharmacological intervention with the aldosterone synthase inhibitor ... the key enzyme in the production of aldosterone is the aldosterone synthase or CYP11B2. CYP11B2 was isolated in 1992 by ... 2 The key enzyme in aldosterone production is aldosterone synthase (CYP11B2). CYP11B2 is predominantly expressed in the adrenal ...
... is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE. ... Aldosterone Synthase: A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of ... Aldosterone Synthase (CYP11B2). Subscribe to New Research on Aldosterone Synthase A mitochondrial cytochrome P450 enzyme that ... 06/01/2006 - "Previous studies have shown that the aldosterone synthase promoter polymorphism -344T/C influences aldosterone ...
... potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial ...
in-licenses aldosterone synthase inhibitors from ElexoPharm GmbH, complementing its ongoing program in chronic kidney disease ... target aldosterone synthase (CYP11B2), a cytochrome P450 enzyme involved in the generation of aldosterone. Reducing aldosterone ... Angion Biomedica Exclusively In-licenses Aldosterone Synthase Inhibitors from ElexoPharm GmbH Complementing its Ongoing Program ... ElexoPharm obtained its aldosterone synthase inhibitors from the lab of Professor Rolf Hartmann, a world-renowned expert in ...
Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or Cytochrome P450C18 or Steroid 18 Hydroxylase ... Inhibition of aldosterone synthase is used as a medical treatment for hypertension, heart failure, and renal disorders. ... It also reviews key players involved in Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or ... The report provides a snapshot of the global therapeutic landscape for Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase ...
... resulting in lack of aldosterone. Structure-function studies have identified aldosterone synthase residues specifically ... Human aldosterone synthase and 11[beta]-hydroxylase: studies on the relationship of structure and function and their clinical ... Fisher, Angela (1999) Human aldosterone synthase and 11[beta]-hydroxylase: studies on the relationship of structure and ... This thesis presents new studies on the relationship between structure and function of aldosterone synthase and 11-hydroxylase ...
Since aldosterone is derived from a final conversion of 18-hydroxycorticosterone into aldosterone by aldosterone synthase, we ... aldosterone synthase inhibitor, 62 ± 2). Conclusions: Local production of aldosterone by its processing enzyme aldosterone ... Detection of aldosterone, as well as its processing enzyme aldosterone synthase, CYP11B2 mRNA, and protein in dorsal root ... Detection of aldosterone, as well as its processing enzyme aldosterone synthase, CYP11B2 mRNA, and protein in dorsal root ...
Aldosterone synthase inhibitors in cardiovascular and renal diseases 529 Relation between aldosterone synthase polymorphism and ... SP285ANGIOTENSIN-CONVERTING ENZYME GENE (ACE), ALDOSTERONE SYNTHASE GENE (CYP11B2) AND ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE ( ... An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated ... Angiotensin II-aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase ...
The major goal of our study was to define the Ang II-induced mechanisms regulating the expression of aldosterone synthase ( ... Angiotensin II (Ang II) is the major physiological regulator of aldosterone production acting acutely to stimulate aldosterone ... Aldosterone is principally synthesized in the zona glomerulosa of the adrenal by a series of enzymatic reactions leading to the ... represent important mechanisms to increase the adrenal capacity to produce aldosterone. ...
Aldosterone Synthase Inhibitors. Decreasing aldosterone synthesis at its enzyme step, aldosterone synthase (AS), CYP11B2, is ... Aldosterone synthase inhibitors (ASI) represent the latest therapeutic strategy to decrease aldosterone production [110]. ... J. Ménard, M.-F. Gonzalez, T.-T. Guyene, and A. Bissery, "Investigation of aldosterone-synthase inhibition in rats," Journal of ... W. B. Lea, E. S. Kwak, J. M. Luther et al., "Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by ...
This study was conducted to assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate ... Relationship Between Aldosterone Synthase CYP1A1 MspI Gene Polymorphism and Prostate Cancer Risk. This study was conducted to ... assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate cancer risk using meta-analysis ...
"Induction of citrate synthase by aldosterone in the rat kidney",. abstract = "The possible induction of renal citrate synthase ... Induction of citrate synthase by aldosterone in the rat kidney. The Journal of Membrane Biology. 1978 Mar 1;41(1):41-64. https ... Law, P-Y & Edelman, IS 1978, Induction of citrate synthase by aldosterone in the rat kidney, The Journal of Membrane Biology ... Law, P-Y., & Edelman, I. S. (1978). Induction of citrate synthase by aldosterone in the rat kidney. The Journal of Membrane ...
We evaluated the influence of C-344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the ... Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis.. Bantis C1, Heering PJ, ... Our results indicate that aldosterone synthase gene C-344T polymorphism not only acts as a risk factor for the development of ...
Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. Journal ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ...
J Renin Angiotensin Aldosterone Syst. 2016 Mar 23;17(1):1470320316633896. doi: 10.1177/1470320316633896. Print 2016 Jan-Mar. ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis.. Xu H1, Wang X2 ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis ...
Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. Molecular and Cellular ... Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. :: Molecular and ... Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. / Nishimoto, Koshiro; ... フィンガープリント Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism の研究トピックを掘り下げ ...
Roumen, L.. / A computational study of the substrate conversion and selective inhibition of aldosterone synthase. Eindhoven : ... Roumen, L 2008, A computational study of the substrate conversion and selective inhibition of aldosterone synthase, Doctor in ... Roumen L. A computational study of the substrate conversion and selective inhibition of aldosterone synthase. Eindhoven: ... Roumen, L. (2008). A computational study of the substrate conversion and selective inhibition of aldosterone synthase. ...
The Aldosterone Synthase Inhibitor FAD286 is Suitable for Lowering Aldosterone Levels in ZDF Rats but not in db/db Mice. ... Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in Human Adrenocortical Cells. ... Aldosterone Synthase Inhibition Improves Glucose Tolerance in Zucker Diabetic Fatty (ZDF) Rats. ... Selectivity of BI 689648, a Novel, Highly Selective Aldosterone Synthase Inhibitor: Comparison with FAD286 and LCI699 in ...
Ogishima T, Mitani F, Ishimura Y. Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity from bovine ... Ogishima, T, Mitani, F & Ishimura, Y 1989, Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity ... Ogishima, T., Mitani, F., & Ishimura, Y. (1989). Isolation of two distinct cytochromes P-45011β with aldosterone synthase ... Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity from bovine adrenocortical mitochondria. In: ...
Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 2013;27:315-24. ... Both CYP11B2 (aldosterone synthase) and CYP11B1 can catalyse the conversion of 11-deoxycorticosterone to corticosterone, ... Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin ... P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Endocrinology. 1998;139: ...
Fig 1⇓ shows the effects of losartan and PD123319 on renin and aldosterone synthase mRNAs in the adrenal cortex in salt- ... In fact, renin mRNA increased by 156±15% (P,.05), but aldosterone synthase mRNA decreased by 384±45% (P,.05). In contrast, ... Effects of losartan and PD123319 on renin mRNA and aldosterone synthase mRNA in salt-restricted nephrectomized rats. Left, ... Prehybridization and hybridization for the aldosterone synthase cytochrome P450 were carried out at 50°C in a buffer containing ...
- Background: Isolated hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency is a rare autosomal recessive disorder linked to aldosterone biosynthesis defect (involving CYP11B2 gene). (eurospe.org)
- Hypoaldosteronism can be caused by defective stimulation of aldosterone secretion, primary defects in adrenal synthesis or secretion of aldosterone, and aldosterone resistance. (empendium.com)
- The therapeutic potential of targeting adrenal steroid synthesis to inhibit aldosterone production has not been fully explored due to the lack of selective aldosterone synthase inhibitors (ASIs). (biomedcentral.com)
- this may be caused by primary adrenal insufficiency , bilateral adrenalectomy, 21-hydroxylase deficiency (leading to hypersecretion of adrenal androgens with reduced production of cortisol and aldosterone), or aldosterone synthase deficiency (leading to isolated hypoaldosteronism). (empendium.com)
- Aldosterone synthase inhibition provides the potential to attenuate both the mineralocorticoid receptor-dependent and independent actions of aldosterone. (biomedcentral.com)
- The effects of LCI699 and eplerenone on cardiac and renal sequelae of aldosterone excess were investigated in a double-transgenic rat (dTG rat) model overexpressing human renin and angiotensinogen. (biomedcentral.com)
- Eplerenone 100 mg increased plasma and 24 h urinary aldosterone while stimulating natriuresis and increasing renin activity. (biomedcentral.com)
- An alternative approach to inhibiting the effects of aldosterone is blocking the renin-angiotensin system (RAS), which decreases aldosterone production indirectly. (biomedcentral.com)
- The different causes of hypoaldosteronism can be differentiated by measurement of plasma renin activity ( PRA ), serum aldosterone levels, and serum cortisol concentrations ( Table 5.1-1 ). (empendium.com)
- In the dTG rat model, LCI699 dose-dependently blocked increases in aldosterone, prevented development of cardiac and renal functional abnormalities independent of blood pressure changes, and prolonged survival. (biomedcentral.com)
- These results provide new insights into the cardiac and renal effects of inhibiting aldosterone synthase in experimental models and translation of the hormonal effects to humans. (biomedcentral.com)
- Hormonal effects of orally administered LCI699 were examined in rat and monkey in vivo models of adrenocorticotropic hormone (ACTH) and angiotensin-II-stimulated aldosterone release, and were compared with the mineralocorticoid receptor antagonist eplerenone in a randomized, placebo-controlled study conducted in 99 healthy human subjects. (biomedcentral.com)
- These experimental data together with growing clinical evidence for the benefits of blocking the actions of aldosterone with mineralocorticoid receptor antagonists (MRAs) in the treatment of heart failure [ 3 ]-[ 5 ] provide the rationale for new therapeutic approaches to inhibit aldosterone production. (biomedcentral.com)
- Type I and type II pseudohypoaldosteronism, potassium-sparing diuretics that compete for the aldosterone receptor (eg, spironolactone and eplerenone) or that close the sodium channels in the luminal membrane (eg, amiloride and triamterene), and certain antibiotics that inhibit the collecting tubule sodium channel (trimethoprim and pentamidine). (empendium.com)
- Selective inhibition of aldosterone synthase appears to be a promising approach to treat diseases associated with aldosterone excess. (biomedcentral.com)
- Causes of hyperkalemia other than endocrine disorders should also be considered, including drugs inhibiting adrenal steroid synthesis (eg, ketoconazole) and, although infrequently, heparin, which reduces the number of angiotensin II receptors in the zona glomerulosa of the adrenal cortex and results in suppression of aldosterone synthesis and hyperkalemia. (empendium.com)
- In vitro studies with recombinant human enzymes showed LCI699 to be a potent, reversible, competitive inhibitor of aldosterone synthase ( K i = 1.4 ± 0.2 nmol/L in humans) with relative selectivity over 11β-hydroxylase. (biomedcentral.com)
- In contrast to eplerenone, LCI699 increased the aldosterone precursor 11-deoxycorticosterone and urinary potassium excretion. (biomedcentral.com)
- Diagnosis is based on clinical history, focusing primarily on the use of medications or presence of diseases that could interfere with aldosterone metabolism and on laboratory findings. (empendium.com)
- Rat and monkey in vivo models of stimulated aldosterone release predicted human dose- and exposure-response relationships, but overestimated the selectivity of LCI699 in humans. (biomedcentral.com)