The renin-angiotensin system

Vallotton, Michel B.

doi:10.1016/0165-6147(87)90013-7

Cited by 193 publications

(97 citation statements)

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“…The renin-angiotensin system (RAS) plays a critical role in blood pressure regulation and in fluid and electrolytes homeostasis; it is also involved in the pathogenesis of many cardiovascular diseases (1,2). The RAS consists of a cascade of enzymatic reactions leading to formation of angiotensin (Ang) II which is a powerful vasoconstrictor.…”

mentioning

confidence: 99%

Pharmacological Profiles of a Novel Non-peptide Angiotensin II Type I Receptor Antagonist HR720 In Vitro and In Vivo

Jin

Song

Oka

et al. 1997

Japanese Journal of Pharmacology

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ABSTRACT-The pharmacological properties of 2-butyl-4-(methylthio)-1- [[2 [[[(propylamino)carbonyl] amino] sulfonyl](1,1 biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo systems. In vitro autoradiography using 125I-[Sar1,IIe8]Ang II as a ligand revealed that HR720 competitively inhibited the specific binding of the ligand to the adrenal cortex. The IC50 value for the adrenal cortex was 1.5 x 10-8 M, and the IC50 for medulla was 1.4 x 10-6 M. Similar results were obtained in the adrenal cortex with CV-11974, a known potent AT1-receptor antagonist. Since AT1 receptors are known to predominate in the adrenal cortex and AT2-receptors in the adrenal medulla, it is considered that HR720 is highly selective for AT, receptors. HR720 inhibited the Ang II-induced contraction of isolated rabbit aortic strips and hu man gastroepiploic arteries in a noncompetitive manner, pD'2=9.40 and 9.62 for rabbit aorta and human artery, respectively. With CV-11974, pD'2 values of 9.84 in isolated rabbit aorta and 10.00 in human artery were obtained. HR720 did not affect the norepinephrine-, serotonin or KCl-induced contraction even at a concentration of 1 x 10-5 M. In anesthetized hamsters, HR720 induced a dose-dependent inhibition of the pressure response to Ang II. The potency of HR720 to antagonize the Ang II-induced pressure response was similar to that of CV-11974. These results demonstrate that HR720 is a potent and selective AT1 -receptor antagonist. Keywords:Renin-angiotensin system, Angiotensin II, Receptor, Antagonist, Isolated vesselThe renin-angiotensin system (RAS) plays a critical role in blood pressure regulation and in fluid and electrolytes homeostasis; it is also involved in the pathogenesis of many cardiovascular diseases (1, 2). The RAS consists of a cascade of enzymatic reactions leading to formation of angiotensin (Ang) II which is a powerful vasoconstrictor. The angiotensin converting enzyme (ACE) inhibitors have clearly demonstrated the beneficial effect of pharmacological inhibition of the RAS in the treatment of hypertension and congestive heart failure (3). Recent studies have suggested that ACE inhibitors effectively prevented the progression of atherosclerosis in high cholesterol loaded rabbit aorta (4, 5) and inhibited the progression of renal damage in the rat model of chronic renal failure (6, 7), indicating the involvement of Ang II in such pathological disorders. However, there are many reports on the unwanted side effects of ACE inhibitors such as cough and angioedema resulting from the lack of * To whom correspondence should be addressed .specificity of ACE inhibitors for Ang I (8, 9). Moreover, ACE inhibitors interfere with the kinin metabolism (10). Recent studies have demonstrated that Ang II can also be formed in non-ACE-dependent manner in several species of animals including humans (11-13). In view of these limitations of ACE inhibitors, selective blocking of Ang I...

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mentioning

confidence: 99%

Pharmacological Profiles of a Novel Non-peptide Angiotensin II Type I Receptor Antagonist HR720 In Vitro and In Vivo

Jin

Song

Oka

et al. 1997

Japanese Journal of Pharmacology

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“…Angiotensin II, through its action on AT 1 -receptors, is a potent vasoconstrictor, 7 and can also increase blood pressure indirectly through activation of the sympathetic nervous system. 8 It is well established, from studies such as the Framingham Study 3 and the Multiple Risk Factors Intervention Trial (MRFIT), 9 that there is a continuous relationship between elevated blood pressure and the risk of cardiovascular events, and that lowering blood pressure reduces the risk of such events.…”

Section: Effects On Blood Pressurementioning

confidence: 99%

The potential role of AT1-receptor blockade in the prevention and reversal of atherosclerosis

Papademetriou

2002

J Hum Hypertens

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The renin-angiotensin system may contribute to the development and progression of atherosclerosis both by increasing blood pressure and by direct effects on all phases of the atherogenic process. Genetic determinants of renin-angiotensin system activation, notably the DD genotype of angiotensin converting enzyme (ACE), are associated with an increased risk of cardiovascular events, as is increased plasma renin activity. In addition, angiotensin II has been shown to increase the uptake and oxidation of low density lipoprotein (LDL) by macrophages and endothelial cells. Angiotensin II also stimulates the production of interleukin 6 and activates the pro-inflammatory factor nuclear factor B , leading to expression of adhesion molecules and recruitment of monocytes and macrophages, and increases the production of pro-coagulatory factors. In

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“…Churchill 1985;Vallotton 1987). This review therefore focuses on the intracellular processes that govern renin release from juxtaglomerular cells.…”

Section: Introductionmentioning

confidence: 99%

Cellular control of renin secretion

Kurtz

Wagner

Reviews of Physiology, Biochemistry and Pharmacology

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The renin-angiotensin system

Cited by 193 publications

References 22 publications

Pharmacological Profiles of a Novel Non-peptide Angiotensin II Type I Receptor Antagonist HR720 In Vitro and In Vivo

Pharmacological Profiles of a Novel Non-peptide Angiotensin II Type I Receptor Antagonist HR720 In Vitro and In Vivo

The potential role of AT1-receptor blockade in the prevention and reversal of atherosclerosis

Cellular control of renin secretion

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