Over the last 2 decades, it has become clear that angiotensin can be generated not only in the systemic circulation but also in multiple tissue sites, where its production can be regulated by local factors. Given the ability of angiotensin II to influence target cell proliferation, hypertrophy, and apoptosis, tissue angiotensin systems potentially play an important role in a wide variety of physiological processes. In this issue of Hypertension, De Mello and Danser1 review the evidence for the synthesis of angiotensin II in the heart and discuss its possible role in health and disease. Their review complements other recent reviews of this subject, such as that by Dostal and Baker.2 Uniquely, however, the present review discusses the potential role of intracellular angiotensin II, called intracrine angiotensin II, in intercellular signaling and calcium flux in the heart. These findings are based on De Mellos studies1 of renin, angiotensin I, and angiotensin II dialyzed into rat cardiac cells. ...
Angiotensin II receptor type 1 or AT1 receptor is the best characterized angiotensin receptor. It has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor antagonists are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure. The AT1 receptor mediates the major cardiovascular effects of angiotensin II. Effects include vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium reuptake, modulation of central sympathetic nervous system activity, cardiac contractility, central osmocontrol and extracellular matrix formation. The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in ...
Nox2-containing NADPH oxidases are reported to be involved in the development of cardiac fibrosis in response to chronic angiotensin II infusion, but the cellular source(s) of Nox2 involved in fibrosis remains unclear. We investigated the role of endothelial Nox2 in angiotensin II-induced left ventricular hypertrophy (LVH). Male transgenic mice with endothelial-specific overexpression of Nox2 were compared with matched wild-type (wt) littermates after angiotensin II (1.1 mg/kg per day) or saline infusion for 14 days. Basal blood pressure and left ventricular NADPH oxidase activity were similar in wt and transgenic mice. After angiotensin II infusion, both wt and transgenic groups developed similar hypertension (170.2±11.6 vs 170.4±12.3 mm Hg; n=10) and hypertrophy (left ventricular/body weight ratio 4.8±0.2 vs 4.7±0.2 mg/g; and echocardiographic septal thickness increased by 34% wt and 37% transgenic mice; n,10). NADPH oxidase activity was higher in angiotensin II-infused transgenic compared ...
The angiotensin II receptors, (AGTR1) and (AGTR2), are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin-angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II. The AT1 and AT2 receptors share a sequence identity of ~30%, but have a similar affinity for angiotensin II, which is their main ligand. The AT1 receptor is the best elucidated angiotensin receptor. The AT1 subtype is found in the heart, blood vessels, kidney, adrenal cortex, lung and brain and mediates the vasoconstrictor effects. The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to Gq/11 and Gi/o and thus activates phospholipase C and increases the cytosolic Ca2+ concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase and ...
Ang II infusion induces an immediate vasoconstrictive response that is typically followed by a gradual recovery despite continued infusion of the pressor agent. The buffering effect on Ang II-induced vasoconstriction is at least in part mediated by vasodilatory PGs, including PGE2.14,16-18 In a previous study, we discovered a novel role of mPGES-1-derived PGE2 in modulating Ang II-induced hypertensive response. In extension of this work, the present study demonstrated that the vasculoprotection of PGE2 is mediated by the suppression of oxidative stress.. Ang II-induced hypertension in mPGES-1−/− mice was completely prevented by Tempol treatment and was fully restored on termination of the antioxidant. Treatment with a second antioxidant, apocynin, produced a similar blood pressure-lowering effect. Apocynin is widely used as an inhibitor of NADPH oxidase19 but was recently found to inhibit vascular oxidative stress via an NADPH oxidase-independent mechanism.20 Together, the similar results ...
1. When the renin-angiotensin system of rats had been suppressed by a high salt diet or by bilateral nephrectomy, large doses of angiotensin II antiserum were required to block the pressor action of exogenous angiotensin II. Infusion of renin profoundly lowered the blocking requirement of such animals.. 2. It is postulated that renin bound to blood vessels generates angiotensin locally which is taken up by vascular receptors. Where such receptors are left unoccupied and free to bind exogenous angiotensin, high doses of blocking antisera are required.. 3. Animals with hypertension produced by renal artery constriction with contralateral nephrectomy were shown to be in positive sodium balance. Nevertheless their blocking requirement was low.. 4. It is suggested that the local generation of angiotensin may play a role in the production of renal hypertension and that this accounts for the development of hypertension even in animals immunized against angiotensin. ...
Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells, kidney epithelial cells, and the brain). Angiotensin II acts on the CNS to increase ADH production, and also acts on venous and arterial vessels smooth muscle to cause vasoconstriction. Angiotensin II also increases Aldosterone secretion, therefore, it acts as an endocrine, autocrine/paracrine, and intracrine hormone.. ACE is a target of ACE inhibitor drugs, which decrease the rate of Angiotensin II production. Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates an IP3-dependent mechanism leading to a rise in intracellular calcium levels and ultimately causing contraction). In addition, angiotensin II acts at the Na/H+ exchanger in the proximal tubules of the kidney to stimulate Na reabsorption and H+ ...
It is now firmly established that inhibition of ACE does have a markedly beneficial effect in the treatment of heart failure. ACE inhibitor therapy, however, does not completely block angiotensin II production, and in some patients, angiotensin II levels remain elevated, in part, because of the conversion of angiotensin I to angiotensin II by chymase activity.29 Thus, continued AT2 receptor stimulation could occur. This hypothesis is indirectly supported by the relative upregulation of the AT2 receptor in human heart failure,30 31 although this finding is controversial.32 33 Currently, no therapeutic agents that specifically act on the AT2 receptor are approved for clinical trials. However, numerous AT1 receptor blockers are available that could hypothetically shunt the activity of the cardiac RAS toward stimulation of the beneficial AT2 receptor.. Two separate clinical approaches evaluate this hypothesis. First, ACE inhibitor therapy was directly compared with AT1 receptor antagonist therapy in ...
TY - JOUR. T1 - Ionophoric Properties of Angiotensin II Peptides. Nuclear Magnetic Resonance Kinetic Studies of the Hormone-Mediated Transport of Manganese Ions Across Phosphatidylcholine Bilayers. AU - Degani, Hadassa. AU - Lenkinski, Robert E.. PY - 1980/1/1. Y1 - 1980/1/1. N2 - The linear peptide hormones angiotensin II and [Asn1, Val5] angiotensin II are found to mediate the transport of Mn(II) ions across phosphatidylcholine bilayers. Nuclear magnetic resonance spectroscopy (NMR) is applied to monitor the rate of transport of Mn(II) ions by measuring the rate of disappearance of the NMR signal of the choline methyl groups of the inner phospholipid layer. This rate of disappearance is analyzed in terms of a pseudo-first-order rate equation for the transport process. The rate of transport of Mn(II) varies linearly with both the concentrations of Mn(II) and angiotensin II (A-II) present, suggesting that the ions are transported in a complex with 1:1 stoichiometry. An analysis of the ...
We studied the effects of intravenous infusion of angiotensin II on the circulation of the fetus in lambs in utero through chronically maintained intravascular catheters. Angiotensin II infused in doses of 29-280 ng/min per kg fetal weight resulted in an increase in plasma angiotensin II from a control value of 87 +/- 17 to 341 +/- 129 (mean +/- SE) pg/ml; these levels are similar to those observed following hemorrhage in fetal lambs. Fetal mean arterial blood pressure increased from 46 +/- 2.0 to 56 +/- 2.7 torr and fetal heart rate increased from 172 +/- 6 to 189 +/- 6 beats/min, an effect which was not altered by beta-adrenergic or cholinergic blockade. Fetal cardiac output and its distribution were measured before and during infusion of angiotensin II by the radionuclide-labeled microsphere technique. Combined ventricular output increased significantly from 526 +/- 32 to 616 +/- 24 ml/min per kg fetal body weight. Angiotensin constricted the umbilical-placental circulation as well as the ...
TY - JOUR. T1 - Vasopressor response to angiotensin II infusion in patients with chronic heart failure receiving β-blockers. AU - Vittorio, Timothy J.. AU - Lang, Chim C.. AU - Katz, Stuart D.. AU - Packer, Milton. AU - Mancini, Donna M.. AU - Jorde, Ulrich P.. PY - 2003/1/21. Y1 - 2003/1/21. N2 - Background - A synergistic interaction between the angiotensin II (Ang II) type 1 receptor and α1-adrenergic receptors has been described. We hypothesized that the nonselective β-antagonist carvedilol, through its α1-adrenergic blocking properties, may modulate vascular reactivity to Ang II in patients with chronic heart failure (CHF). Accordingly, we compared the vasopressor response to infused Ang II in patients treated with carvedilol and metoprolol, a selective β-antagonist. Methods and Results - All subjects were treated with carvedilol or metoprolol for at least 3 months. ACE inhibitor therapy was standardized to enalapril 40 mg/d or the maximally tolerated dose. Exogenous Ang II was ...
The rennin-angiotensin II system (RAS) and the insulin-PI3kinase signalling pathways cross-interact with important physiological and pathophysiological consequences for cells and the whole organism. Here, the effect of 24 h pre-incubation of EA.hy926 with two different concentrations of angiotensin II, on insulin-mediated activation of the PI3kinase-AKT-eNOS signalling was investigated. Quiescent EA.hy926 cells were treated with insulin (100 nM, 30 min) following 24 h pre-treatment with or without either 0.1 or 1 µM of angiotensin II. Cell lysates were immunoblotted for phospho AKT Ser-473, phospho eNOS Ser-1177 and normalized with β-actin. Homogenates of EA.hy926 treated with insulin in the presence or absence of 1 µM angiotensin II, were also subjected to nitric oxide synthase (NOS) activity assay using titrated arginine as substrate. To exclude cytotoxicity of the 1 µM angiotensin II concentration, Trypan blue cell viability assay as well as the microscopic examination of
The examination of synthetic valyl-5-angiotensin II-amide in the conscious dog revealed the following:. 1. Both the arterial and the central venous pressure responses exhibit tachyplylaxis when high doses of angiotensin II are administered, althoug not when medium or low doses are given. Cross-tachyphylaxis can be demonstrated between renin and angiotensin II but not between either of these and norepinephrine. These results suggest that tachyphylaxis to renin is due to tachyphylaxis to angiotensin.. 2. Angiotensin II and norepinephrine provoke a dose-dependent increase in central venous pressure. The threshold dose is about 10 times higher than that necessary for the effect on arterial pressure. In doses eliciting the same increase of arterial blood pressure, norepinephrine is about twice as active on the venous pressure as angiotensin II.. 3. Anesthesia and atropinization both reduce or abolish the effect of angiotensin II as well as that of norepinephrine on the venous pressure, indicating the ...
Methods and Results-Mice infused with angiotensin II showed a marked increase in interleukin-12p35 expression in cardiac macrophages. The degree of cardiac fibrosis was significantly enhanced in interleukin-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to angiotensin II. Fibrotic hearts of p35-KO mice showed increased accumulation of alternatively activated (M2) macrophages and expression of M2 genes such as Arg-1 and Fizz1. Bone marrow-derived macrophages from WT or p35-KO mice did not differ in differentiation in response to angiotensin II treatment; however, in the presence of CD4+ T cells, macrophages from p35-KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factor-β. Moreover, CD4+ T-cell-treated p35-KO macrophages could stimulate cardiac fibroblasts to differentiate into α-smooth muscle actin-positive and collagen I-positive myofibroblasts in 3-dimensional nanofiber gels. Neutralizing antibodies against ...
1. This study was designed to quantify the role of angiotensin II in determining the chronic relationships between arterial pressure, renal haemodynamics and sodium excretion.. 2. In six control dogs sodium balance was achieved during chronic increases in sodium intake from 5 to 495 mmol/day with small increases in arterial pressure (7mmHg), moderate increases in glomerular filtration rate (19%) and decreases in filtration fraction. Similar increases in sodium intake in dogs whose circulating levels of angiotensin II were fixed, due to a constant intravenous infusion of 4.85 pmol of angiotensin II min−1 kg−1, caused large increases in arterial pressure (42%), glomerular filtration rate (31%), filtration fraction and calculated renal sodium reabsorption above control. In six dogs whose angiotensin II formation was blocked by SQ 14 225, sodium balance at intakes of 5-80 mmol/day occurred at reduced arterial pressure, glomerular filtration rate, filtration fraction and sodium reabsorption ...
1. Competitive or non-competitive inhibition of the myotropic and pressor response of angiotensin II is dependent on the nature of the substituent in position 8 of the antagonist peptide analogue. Substituents in other positions of the molecule, particularly position 1, contribute greatly to the potency of these antagonists.. 2. As is evidenced after adrenalectomy or after blockade with phentolamine and phenoxybenzamine, the initial pressor activity observed with all the antagonistic peptides is partially due to the release of catecholamines and partially to a direct myotropic effect.. 3. [Sar1, Thr8]angiotensin II has been found to possess the lowest agonist to antagonist ratio of all antagonists tested.. 4. [Des-Asp1, Ile8]angiotensin II selectively and specifically inhibits the release of aldosterone from adrenal cortex. Thus, unlike angiotensin II, this heptapeptide has pronounced organ specificity, suggesting that the heptapeptide (angiotensin III) is the aldosterone-releasing ...
Peptides , Angiotensins and Related Peptides , Angiotensin II, human; The octapeptide angiotensin II (Ang II) exerts a wide range of effects on the cardiovascular system. It is also implicated in the regulation of cell proliferation, fibrosis and apoptosis. Ang II is formed by cleavage of Ang I by the angiotensin-converting enzyme (ACE) or chymases. Human heart chymase, a chymotrypsin-like serine proteinase, hydrolyzes the Phe8-His9 bond to yield the octapeptide hormone angiotensin II and His-Leu.; DRVYIHPF; H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH
TY - JOUR. T1 - Downregulation of vascular angiotensin II type 1 receptor by thyroid hormone. AU - Fukuyama, Kae. AU - Ichiki, Toshihiro. AU - Takeda, Kotaro. AU - Tokunou, Tomotake. AU - Iino, Naoko. AU - Masuda, Satoko. AU - Ishibashi, Minako. AU - Egashira, Kensuke. AU - Shimokawa, Hiroaki. AU - Hirano, Katsuya. AU - Kanaide, Hideo. AU - Takeshita, Akira. PY - 2003/3/1. Y1 - 2003/3/1. N2 - Thyroid hormone has a broad effect on cardiovascular system. 3,3′,5-triiodo-L-thyronine (T3), a biologically active form of thyroid hormone, increases cardiac contractility. T3 causes arterial relaxation and reduction of systemic vascular resistance, resulting in an increase in cardiac output. However, the molecular mechanisms of vascular relaxation by T3 are incompletely characterized. We studied the effect of T3 on the angiotensin (Ang) II type 1 receptor (AT1R) expression in vascular smooth muscle cells. T3 dose-dependently decreased expression levels of AT1R mRNA, with a peak at 6 hours of ...
ABSTRACT. Angiotensin II (Ang II) is a critical component of the renin-angiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were not changed. However, the aggregation response to collagen was reduced in isolated ...
Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were _disibledevent=font-size:10pt;line-height:1.5;font-family:Verdana;>5-HT in platelets, an event
TY - JOUR. T1 - Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels AU - Dimitropoulou, Christiana. AU - White, Richard E.. AU - Fuchs, Leslie. AU - Zhang, Hanfang. AU - Catravas, John D.. AU - Carrier, Gerald O.. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet paradoxically. Ang II may dilate certain vascular beds via an undefined mechanism. Ang II-induced vasoconstriction is mediated by the AT 1 receptor, whereas the relative expression and functional importance of the AT 2 receptor in regulating vascular resistance and blood pressure are unknown. We now report that Ang II induces relaxation of mesenteric microvessels and that this vasodilatory response was unaffected by losartan, an AT 1 receptor antagonist, but was inhibited by PD123.319. a selective antagonist of AT 2 receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT ...
TY - JOUR. T1 - Impaired pulmonary conversion of angiotensin I to angiotensin II in rats exposed to chronic hypoxia. AU - Jackson, Robert. AU - Narkates, A. J.. AU - Oparil, S.. PY - 1986/1/1. Y1 - 1986/1/1. N2 - The effects of exposing rats to hypoxia at normal atmospheric pressure for periods of 21-24 days on intrapulmonary conversion of angiotensin I (ANG I) to angiotensin II (ANG II) were examined using an isolated rat lung preparation perfused at constant flow. 125I-ANG I (160 fmol) was injected alone and with graded doses (0.1, 1.0, and 100 nmol) of unlabeled ANG I into the pulmonary artery, and the effluent was collected for measurement of ANG I, ANG II, and metabolites. At low doses of injected ANG I (125I-ANG I alone or with 0.1 to 1.0 nmol unlabeled ANG I), the percent conversion of ANG I to ANG II was 67.5 ± 2.1 (SE), 65.1 ± 2.0, and 62.5 ± 1.6 in 21-day hypoxia-exposed animals and 83.8 ± 2.7, 81.4 ± 3.9, and 79.6 ± 2.3 (P , 0.01) in control rats maintained under normoxic ...
Szekeres, Mária and Nádasy, György László and Turu, Gábor and Soltész-Katona, Eszter and Benyó, Zoltán and Ruisanchez, Éva and Szabó, Eszter and Takáts, Zoltán and Bátkai, Sándor and Tóth, Zsuzsanna E. and Hunyady, László (2015) Endocannabinoid-mediated modulation of G protein-coupled receptor signaling-induced vasoconstriction and hypertension. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 403C. pp. 46-56. ISSN 0303-7207 Gyires, Klára and Rónai, András Z and Zádori, Zoltán S and Tóth, Viktória E and Németh, József and Szekeres, Mária and Hunyady, László (2014) Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats. Molecular and cellular endocrinology, 382 (2). pp. 971-8. ISSN 1872-8057 Gyires, Klára and Rónai, Z. András and Zádori, Zoltán Sándor and Tóth, Viktória E. and Németh, József and Szekeres, Mária and Hunyady, László (2014) Angiotensin II-induced activation of central AT1 receptors ...
Infusion of angiotensin II continuously into the renal artery of conscious dogs led to a modest increase in arterial pressure that was associated in the steady state with increased total peripheral resistance. The dose of angiotensin II used (0.5 ng ⋅ kg−1 ⋅ min−1) was subpressor acutely (both over the 1st h and at 24 h) and reduced renal blood flow by about 15% during the 1st h of infusion. Onday 7 of the angiotensin II infusion, mean arterial pressure was still close to preinfusion values, and an increase in resting arterial pressure was observed only fromday 14 onward, with the elevation in arterial pressure being well maintained for the rest of the infusion period.. Evidence that the hypertension was due to the intrarenal actions of angiotensin II is provided by comparison with the effects of intravenous angiotensin II infusion at the same dose in the same dogs. Intravenous infusion of angiotensin II did not alter arterial pressure, and there were no significant changes in total ...
Angiotensin II - Get up-to-date information on Angiotensin II side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Angiotensin II
We identified an angiotensin-generating system in pancreatic islets and found that exogenously administered angiotensin II, after binding to its receptors (angiotensin II type 1 receptor [AT1R]), inhibits insulin release in a manner associated with decreased islet blood flow and (pro)insulin biosynthesis. The present study tested the hypothesis that there is a change in AT1R expression in the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db mouse, which enables endogenous levels of angiotensin II to impair islet function. Islets from 10-week-old db/db and control mice were isolated and investigated. In addition, the AT1R antagonist losartan was administered orally to 4-week-old db/db mice for an 8-week period. We found that AT1R mRNA was upregulated markedly in db/db islets and double immunolabeling confirmed that the AT1R was localized to beta-cells. Losartan selectively improved glucose-induced insulin release and (pro)insulin biosynthesis in db/db islets. Oral ...
Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet paradoxically. Ang II may dilate certain vascular beds via an undefined mechanism. Ang II-induced vasoconstriction is mediated by the AT1 receptor, whereas the relative expression and functional importance of the AT2 receptor in regulating vascular resistance and blood pressure are unknown. We now report that Ang II induces relaxation of mesenteric microvessels and that this vasodilatory response was unaffected by losartan, an AT1 receptor antagonist, but was inhibited by PD123.319. a selective antagonist of AT2 receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT2 receptor mRNA in smooth muscle from these same microvessels. Ang II-induced relaxation was inhibited by either tetraethylammonium or iberiotoxin, suggesting involvement of the large-conductance, calcium- and voltage-activated potassium (BKCa) channel. Subsequent whole-cell and single-channel patch-clamp
UNLABELLED Angiotensin II has articularly shown to play a key role in the regulation of inflammatory processes in hypertension. AIM The present study aims to correlate the angiotensin II-induced hypertension 4th systemic inflammation. MATERIAL AND METHODS We conducted an experimental study on Wistar male rats who received Ang II via subcutaneous miniosmotic pumps for 2 weeks. Rats were exposed to a 12h light /12h dark cycle. Sham rats were used as control. Systolic load pressure measurements and a flow cytometric analysis of lymphocyte surface markers were performed. After 14 days, the animals were euthanized under anesthesia with ylazine/ketaniine. RESULTS Systolic BP progressively and significantly increased in rats 4th Ang II chronic infusion. We observed a statistical significant difference (p = 0.00001), in terms of T lymphocytes percentage between control rats plasma and Ang H treated rats lasma, in 14 days. CONCLUSIONS Angiotensin II is an important mediator of hypertension and directly
New Report on Angiotensin II Receptor Type 1 (AT1 Receptor) Inhibitors-Pipeline Insights, 2017 added to fshlxkc.cn store which has 60 pages and available for purchase at US $ 1250.
BACKGROUND AND PURPOSE Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. EXPERIMENTAL APPROACH AngII was infused (1.44 mg · kg(-1) · day(-1), s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti-TLR4 antibody or IgG (1 μg · day(-1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells (VSMC) from hypertensive rats (SHR). KEY RESULTS Aortic TLR4 mRNA levels were raised by AngII infusion. Anti-TLR4 antibody treatment of AngII-treated mice
... definition, any of three oligopeptides occurring in plasma, an inactive form (angiotensin I) and two varieties (angiotensin II and angiotensin III) that elevate blood pressure and stimulate the adrenal cortex to secrete aldosterone. See more.
INTRODUCTION: Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin-aldosterone-system, causes the formation of reactive oxygen species and DNA damage in kidneys and hearts of hypertensive mice. To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin-aldosterone-system on angiotensin II-induced genomic damage were studied. METHODS: In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker candesartan, the mineralocorticoid receptor blocker eplerenone and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis. RESULTS: Administration of ...
TY - JOUR. T1 - Increased Vascular Sensitivity to Angiotensin II in Psychosocial Hypertensive Mice. AU - Clinton Webb, R.. AU - Johnson, Joyce C.. AU - Vander, Arthur J.. AU - Henry, James P.. PY - 1983/1/1. Y1 - 1983/1/1. N2 - CBA mice develop hypertension when placed in complex population cages that facilitate social interactions and competition for territory. After 1 month, these mice have normal plasma renin levels, but blockade of converting enzyme lowers blood pressure to normal. To test the possibility that this normal-renin hypertension is caused by enhanced pressor responsiveness to angiotensin II (All), we examined the effects of All on hindquarter and renal vasculatures from 13 hypertensive and 13 normotensive mice. Both vascular beds were pump-perfused at a constant flow with plasma substitute. Optimal perfusion flows and basal pressures were similar in hindquarter (8 ml/100 g/min; 60 mm Hg) and renal vasculatures (130 ml/100 g/min; 50 mm Hg) from normotensive and hypertensive mice. ...
There is no question that angiotensin II can play its enhancing effects on the sympathetic nervous system at various levels and that not only a presynaptic potentiation of norepinephrine secretion but also an amplification of the responsiveness of adrenergic receptors to neural stimuli is involved as indicated by the data of Lyons et al.R1 In a study we performed several years ago in humans,R2 we also suggested this to be the case because in hypertensive patients both acute and long-term ACE inhibition attenuated the reflex increase in forearm vascular resistance due to unloading of cardiac receptors without any concomitant alteration of the reflex increase in plasma norepinephrine.. There is also no question that the enhancing effect of angiotensin II on sympathetic cardiovascular influences is reciprocated because sympathetic nerve activity is an important determinant of renal secretion of reninR3 R4 and thus of the activity of the renin-angiotensin system. It is certainly possible, on the ...
PubMed journal article: Effect of angiotensin-converting enzyme two-week inhibition on renal angiotensin II receptors and renal vascular reactivity in SHR. Download Prime PubMed App to iPhone, iPad, or Android
Angiotensin-II receptor antagonists work in a similar way to ACE inhibitors. But instead of stopping the production of angiotensin II, they block its action. This allows the blood vessels to expand, improving blood flow and reducing blood pressure. Angiotensin II is a very potent chemical that causes muscles surrounding blood vessels to contract, thereby narrowing blood vessels. This narrowing increases the pressure within the vessels and can cause high blood pressure (hypertension). Angiotensin II receptor blockers (ARBs) are medications that block the action of angiotensin II by preventing angiotensin II from binding to angiotensin II receptors on blood vessels. As a result, blood vessels enlarge (dilate) and blood pressure is reduced. Reduced blood pressure makes it easier for the heart to pump blood and can improve heart failure. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed. ARBs have effects that are similar to angiotensin converting enzyme ...
In this study we demonstrate that angiotensin II deteriorates glucose metabolism through deleterious effects on pancreatic β-cell mitochondrial function and insulin secretion. This effect involves IL-1β- and NF-κB-mediated inflammation and apoptosis and is independent of changes in blood pressure and insulin sensitivity.. In vivo infusion of angiotensin II for 4 weeks completely abolished glucose-stimulated insulin secretion. Surprisingly, after isolation and culturing, islets from angiotensin II-treated mice showed similar insulin secretion upon glucose stimulation as islets from saline-infused mice. Several possibilities can explain this finding: Angiotensin II-induced damage is reversible, and the islets had recovered between isolation and the insulin secretion assay. Alternatively, the in vivo deleterious effect of angiotensin II may be mediated via immune cells, which are lost following islet isolation. This would explain the discrepancy between the mild, direct in vitro effects of ...
To investigate whether apocynin, a NADPH oxidase inhibitor, produced cardioproteictive effects in Ang II-induced hypertensive mice, and to elucidate the underlying mechanisms. C57BL/6 mice were subcutaneously infused Ang II for 4 weeks to mimic
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 ...
Angiotensin II acts through two separate receptors namely AT1 and AT2. Two AT1 receptor subtypes (AT1A and AT1B) have been described. FEBS Lett. 1992 Feb 24;298(2-3):257-60. AT1 receptors are distributed widely in tissues including the adipose tissue as well as vasculature, heart, kidney, brain, liver, adrenal gland and lung. Am J Hypertens. 2000 Jan;13(1 Pt 2):31S-38S. The classic effects of Angiotensin II namely vasoconstriction, as well as aldosterone stimulation from the adrenal gland with sodium and water reabsorption in the kidneys are mediated through the AT1 receptors. Pharmacol Rev. 1993 Jun;45(2):205-51. AT2 receptor expression which is initially widespread in the foetus, decreases post-natally and remains expressed in the adipose tissue as well as the vasculature, heart, adrenal gland, pancreas and female reproductive organs. Am J Hypertens. 2000 Jan;13(1 Pt 2):31S-38S. Angiotensin seems to act on AT2 receptors to produce effects totally opposed to those mediated by the AT1 receptor ...
... human diseases including hypertension however commonly employed antioxidants have proven ineffective in clinical trials. SOD2 depletion with siRNA increased both basal and angiotensin II-stimulated cellular O2?. Treatment of mice in vivo with mitoTEMPO attenuated hypertension when ABT-751 given at the onset of ABT-751 angiotensin II infusion and decreased blood pressure by 30 mm Hg following establishment of both angiotensin II-induced and DOCA-salt hypertension while a similar dose of non-targeted TEMPOL was not effective. In vivo mitoTEMPO decreased vascular O2? increased vascular NO? production and improved ABT-751 endothelial-dependent relaxation. Interestingly transgenic mice overexpressing mitochondrial SOD2 exhibited attenuated angiotensin II-induced hypertension and vascular oxidative stress much like mice treated with mitoTEMPO. Conclusions: These studies show that mitochondrial O2? is usually important for the ...
The brain Renin Angiotensin System (RAS) is quickly becoming recognized as a critical mediator of blood pressure and body fluid homeostasis. In the forebrain, the median preoptic nucleus (MnPO) responds to Angiotensin II (Ang II) stimulation by increasing thirst and blood pressure. Understanding how this nuclei regulates blood pressure and body fluid homeostasis in response to Ang II has the potential to open new therapeutic avenues for treatment of hypertension. In the studies following series of studies I investigated the role of MnPO Angiotensin Type Ia receptors in the sustained hypertension induced by Chronic Intermittent Hypoxia (CIH) and thirst regulation. The first project focuses on the role of the MnPO in the sustained hypertension of CIH. Sleep apnea leads to hypertension that persists throughout the waking period. The neural mechanisms that underlie this pathophysiological increase in blood pressure are not well known. CIH is a model of the hypoxemia experienced by sleep apnea sufferers.
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Adult male mongrel dogs were placed on LS (0.05% sodium chloride) for 2 weeks. Body weight (25.4±0.4 to 23.6±0.4 kg), left ventricular systolic pressure (137.0±3.4 to 124.0±6.7 mm Hg), and mean aortic pressure (111±3.1 to 98±4.3 mm Hg) decreased. Plasma angiotensin II concentration increased (4.4±0.7 to 14.8±3.7 pg/mL). Veratrine-induced (5 µg/kg) NO-mediated vasodilation was inhibited by 44% in LS; however, the simultaneous intravenous infusion of ascorbic acid or apocynin acutely and completely reversed this inhibition. In LS heart tissues, lucigenin chemiluminescence was increased 2.3-fold to angiotensin II (10-8 mol/L), and bradykinin (10-4 mol/L) induced reduction of myocardial oxygen consumption in vitro was decreased (40±1.3% to 16±6.3%) and completely restored by coincubation with tiron, tempol or apocynin. Switching of substrate uptake from free fatty acid to glucose by the heart was observed (free fatty acid: 8.97±1.39 to 4.53±1.12 µmol/min; glucose: 1.31±0.52 to ...
The 1166 A/C polymorphism of the angiotensin II type 1 receptor gene does not correlate with the blood pressure response to angiotensin II in patients with CHF Academic Article ...
This gene encodes a transmembrane protein localized to the plasma membrane and perinuclear vesicular structures. The gene product interacts with the angiotensin II type I receptor and negatively regulates angiotensin II signaling. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008 ...
Introduction and Objectives: We have demonstrated previously that angiotensin II (AngII) induces ascending and abdominal aortic aneurysms (AA) in C57BL/6 mice. In an experimental mouse model of Marfans Syndrome that expresses Fbn1C1039G/+, ascending AAs were prevented by both a neutralizing antibody to transforming growth factor-β (TGF-β) signaling and the Ang II receptor antagonist, losartan. Conversely, it has been recently reported that a neutralizing TGF-β antibody leads to abdominal aortic rupture during AngII infusion. The aim of this study was to determine the effects of a TGF-β neutralizing antibody on AngII-induced ascending and abdominal AA formation in normolipidemic mice.. Methods and Results: Eight week old, male, C57BL/6 mice were fed a normal laboratory diet and infused subcutaneously with AngII (1,000 ng/kg/min) by osmotic mini-pumps for 28 days. Mice were injected intraperitoneally with control IgG (R&D Systems, AB-105-C, 10 mg/kg twice a week), or TGF-β IgG antibody (R&D ...
TY - JOUR. T1 - Role of angiotensin II and α-adrenergic receptors during estrogen-induced vasodilation in ewes. AU - Davis, L. E.. AU - Magness, R. R.. AU - Rosenfeld, C. R.. PY - 1992/1/1. Y1 - 1992/1/1. N2 - Estradiol-17β (E2β) produces uterine and systemic vasodilation in nonpregnant ewes without altering mean arterial pressure (MAP). Mechanisms responsible for maintaining MAP and thus uterine blood flow (UBF) may include activation of the renin-angiotensin and/or adrenergic systems. We therefore investigated the effects of systemic blockade of angiotensin II (ANG II) and/or α-adrenergic receptors in nonpregnant, castrated ewes, using saralasin (Sar) and/or phentolamine (Phen) in the presence or absence of intravenous E2β (1.0 μg/kg). In nonestrogenized ewes neither antagonist alone had substantial cardiovascular effects; however, Sar + Phen decreased systemic vascular resistance (SVR) 20 ± 7.4% (SE) and increased heart rate (HR) 50 ± 19% (P , 0.01); MAP and UBF were unaffected. ...
Peptides , Angiotensins and Related Peptides , ClearPoint Angiotensin II, human, 13C and 15N-labeled; The octapeptide angiotensin II (Ang II) exerts a wide range of effects on the cardiovascular system. It is also implicated in the regulation of cell proliferation, fibrosis and apoptosis. Ang II is formed through cleavage of Ang I by the angiotensin-conve; DRVY-I*-HPF [I*= I(U13C6,15N)]; H-Asp-Arg-Val-Tyr-*Ile-His-Pro-Phe-OH [Ile*= Ile(U13C6,15N)]
TY - JOUR. T1 - Angiotensin II reduces mitochondrial content in skeletal muscle and affects glycemic control. AU - Mitsuishi, Masanori. AU - Miyashita, Kazutoshi. AU - Muraki, Ayako. AU - Itoh, Hiroshi. PY - 2009/3. Y1 - 2009/3. N2 - OBJECTIVE-Blockade of angiotensin (Ang) II has been shown to prevent new-onset type 2 diabetes. We focused on the effects of AngII on muscle mitochondria, especially on their biogenesis, as an underlining mechanism of type 2 diabetes. RESEARCH DESIGN AND METHODS-C2C12 cells and C57bl/6 mice were used to examine roles for AngII in the regulation of muscle mitochondria and to explore whether the effect was mediated by type 1 AngII receptor (AT1R) or type 2 receptor (AT2R). RESULTS-C2C12 cells treated with 10-8-10 -6 mol/l AngII reduced the mitochondrial content associated with downregula- tion of the genes involved in mitochondrial biogenesis. The action of AngII was diminished by blockade of AT2R but not AT1R, whereas overexpression of AT2R augmented the effect. ...