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.Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Receptor, Angiotensin, Type 2: An angiotensin receptor subtype that is expressed at high levels in fetal tissues. Many effects of the angiotensin type 2 receptor such as VASODILATION and sodium loss are the opposite of that of the ANGIOTENSIN TYPE 1 RECEPTOR.Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Angiotensin II Type 1 Receptor Blockers: Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.Angiotensin III: A heptapeptide formed from ANGIOTENSIN II after the removal of an amino acid at the N-terminal by AMINOPEPTIDASE A. Angiotensin III has the same efficacy as ANGIOTENSIN II in promoting ALDOSTERONE secretion and modifying renal blood flow, but less vasopressor activity (about 40%).Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.TetrazolesRenin-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.Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.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.Enalaprilat: The active metabolite of ENALAPRIL and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Teprotide: A synthetic nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) which is identical to the peptide from the venom of the snake, Bothrops jararaca. It inhibits kininase II and ANGIOTENSIN I and has been proposed as an antihypertensive agent.Angiotensin II Type 2 Receptor Blockers: Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.Angiotensins: Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Lisinopril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.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.Biphenyl CompoundsPerindopril: An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Cilazapril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat.Saralasin: An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.1-Sarcosine-8-Isoleucine Angiotensin II: An ANGIOTENSIN II analog which acts as a highly specific inhibitor of ANGIOTENSIN TYPE 1 RECEPTOR.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.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.ThiazepinesTetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Rats, Inbred SHR: A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.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.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Renal Circulation: The circulation of the BLOOD through the vessels of the KIDNEY.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Rats, Inbred WKY: A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Hypertension, Renal: Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent.3-Mercaptopropionic Acid: An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Diet, Sodium-Restricted: A diet which contains very little sodium chloride. It is prescribed by some for hypertension and for edematous states. (Dorland, 27th ed)Hypertension, Renovascular: Hypertension due to RENAL ARTERY OBSTRUCTION or compression.Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Imidazolidines: Compounds based on reduced IMIDAZOLINES which contain no double bonds in the ring.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Oligopeptides: Peptides composed of between two and twelve amino acids.Angiotensin Amide: The octapeptide amide of bovine angiotensin II used to increase blood pressure by vasoconstriction.Diuretics: Agents that promote the excretion of urine through their effects on kidney function.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Aorta: The main trunk of the systemic arteries.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.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.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Benzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Chymases: A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Kinetics: The rate dynamics in chemical or physical systems.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Heart: The hollow, muscular organ that maintains the circulation of the blood.Dipeptides: Peptides composed of two amino acid units.Organ Size: The measurement of an organ in volume, mass, or heaviness.Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Natriuresis: Sodium excretion by URINATION.Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.Benzazepines: Compounds with BENZENE fused to AZEPINES.Albuminuria: The presence of albumin in the urine, an indicator of KIDNEY DISEASES.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Kidney Cortex: The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Angioedema: Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Drinking: The consumption of liquids.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Nephrectomy: Excision of kidney.Mineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.Hypertrophy: General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).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)Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.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.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.NADPH Oxidase: A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.Aorta, Thoracic: The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Diuresis: An increase in the excretion of URINE. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Vasopressins: Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.Sodium Chloride: A ubiquitous sodium salt that is commonly used to season food.Subfornical Organ: A structure, situated close to the intraventricular foramen, which induces DRINKING BEHAVIOR after stimulation with ANGIOTENSIN II.CreatinineDrug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.Renal Artery Obstruction: Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Mice, Inbred C57BLOxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Sodium, Dietary: Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Fumarates: Compounds based on fumaric acid.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)Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Arginine Vasopressin: The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.Kidney Tubules, Proximal: The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.Glutamyl Aminopeptidase: A ZINC-dependent membrane-bound aminopeptidase that catalyzes the N-terminal peptide cleavage of GLUTAMATE (and to a lesser extent ASPARTATE). The enzyme appears to play a role in the catabolic pathway of the RENIN-ANGIOTENSIN SYSTEM.Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.Sodium Chloride, Dietary: Sodium chloride used in foods.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d 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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Thirst: A drive stemming from a physiological need for WATER.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Arteries: The vessels carrying blood away from the heart.Forearm: Part of the arm in humans and primates extending from the ELBOW to the WRIST.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Dilleniaceae: A plant family of the order Dilleniales, subclass Dilleniidae, class Magnoliopsida.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.PyridazinesSodium Chloride Symporter Inhibitors: Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Atenolol: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.Juxtaglomerular Apparatus: A complex of cells consisting of juxtaglomerular cells, extraglomerular mesangium lacis cells, the macula densa of the distal convoluted tubule, and granular epithelial peripolar cells. Juxtaglomerular cells are modified SMOOTH MUSCLE CELLS found in the walls of afferent glomerular arterioles and sometimes the efferent arterioles. Extraglomerular mesangium lacis cells are located in the angle between the afferent and efferent glomerular arterioles. Granular epithelial peripolar cells are located at the angle of reflection of the parietal to visceral angle of the renal corpuscle.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Blood Vessels: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Capillary Resistance: The vascular resistance to the flow of BLOOD through the CAPILLARIES portions of the peripheral vascular bed.Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Infusion Pumps, Implantable: Implanted fluid propulsion systems with self-contained power source for providing long-term controlled-rate delivery of drugs such as chemotherapeutic agents or analgesics. Delivery rate may be externally controlled or osmotically or peristatically controlled with the aid of transcutaneous monitoring.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.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.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.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Desoxycorticosterone: A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Arginine: An essential amino acid that is physiologically active in the L-form.Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Injections, Intraventricular: Injections into the cerebral ventricles.
  • In addition, because of cross-talk between different signalling pathways, hyperglycaemia induced PKC activation augments biochemical responses triggered by other pathophysiological mechanisms-for example, hypoxia, 9 shear stress and raised capillary pressure, and/or increased activity of the local renin-angiotensin system. (bmj.com)
  • The experiment was carried out using the Beckman PACE system and steps were taken to determine (a) the migration profiles of angiotensin and its yielded peptides, (b) the minimal amount of angiotensin II detected, (c) the use of different electrolytes and (d) the concentration of inhibitor. (ox.ac.uk)
  • 4 - 7 Although the classically recognized functions of the RAS to promote renal sodium retention and vasoconstriction are mediated through the binding of angiotensin II (Ang II) to type 1 angiotensin (AT 1 ) receptors, 8 , 9 other peptides, enzymes, and receptors in this cascade have received increased scrutiny for their independent contributions to developmental biology, renal and vascular function, and immunity. (asnjournals.org)
  • Indeed, cell lineages that constitute the immune system have the capacity to express RAS components, 11 , 12 and the effects of the RAS peptides and enzymes on inflammatory responses are quite diverse. (asnjournals.org)
  • Data in the literature 1 have shown that the load conditions and neurohumoral systems, among which the renin-angiotensin-aldosterone system (RAAS) stands out, modulate the characteristics of left ventricular hypertrophy that develop in the presence of chronic pressure overload. (scielo.br)
  • In contrast, the clinical trials with renin-angiotensin-aldosterone system (RAAS) blockade versus other antihypertensive agents in primary prevention of DN have provided conflicting results and are confounded, when albuminuria (urinary albumin excretion rate) is the primary outcome, by the rapid but reversible decreases in urinary albumin excretion rate and by the differences in blood pressure control. (diabetesjournals.org)
  • As an example of this wealth of data, in this issue of CMAJ , Pilote and colleagues 2 use administrative databases of hospital discharges and prescription claims to study the comparative effectiveness of angiotensin-converting-enzyme (ACE) inhibitors in the treatment of congestive heart failure. (cmaj.ca)
  • 3 Adding and removing PO 4 groups to intracellular proteins, via kinases and phosphatases respectively, is an important regulatory system for activating and deactivating tissue enzymes, receptor pathways, and transcription factors controlling gene expression. (bmj.com)
  • PKC is not a single enzyme, but rather a family of structurally and functionally related proteins (isoenzymes) derived from multiple genes (at least three) and from alternative splicing of single mRNA transcripts. (bmj.com)
  • Reactive oxygen species (ROS) and free (decompartmentalized) metal ions were identified as key participants in the Maillard reaction, and chelators were identified as potent inhibitors of browning and cross-linking of proteins by glucose. (diabetesjournals.org)
  • Additionally we are shipping Angiotensin I Converting Enzyme 1 Kits (134) and Angiotensin I Converting Enzyme 1 Proteins (25) and many more products for this protein. (antibodies-online.com)
  • Other theoretical options include subthreshold or low-dose paracetamol, cyclooxygenase-2 inhibitors, pre-medication with antihistamines with or without a leukotriene receptor antagonist, co-administration of prostaglandin E2 analogue, traditional Chinese medicine, or desensitisation if antipyretics are deemed desirable. (hkmj.org)
  • ACE inhibitors were also associated with a decrease in pneumonia related mortality, but the data lacked strength. (bmj.com)
  • Because glycoprotein IIb/IIIa inhibitors (abciximab) as adjunctive pharmacological therapy for primary percutaneous coronary intervention in STEMI demonstrated a moderate reduction in mortality at 30 days (2.4% versus 3.4%, P =0.047), we found a similar beneficial result in short-term mortality of cilostazol-based triple therapy in this article (in-hospital death: 2.2% versus 3.4%, P =0.022). (ahajournals.org)