Angiotensin-(1-7) Attenuates Vasoconstriction Evoked by Angiotensin II but Not by Noradrenaline in Man

Abstract

Abstract-Angiotensin-(1-7) has been suggested to be a novel vasodilating peptide. We investigated the direct vascular effect of angiotensin-(1-7) in human forearm resistant vessels, particularly with regard to the interaction with angiotensin II, in healthy normotensive men by strain-gauge venous occlusion plethysmography with intra-arterial infusions of peptides. Intra-arterial infusion of angiotensin-(1-7) at 0.1 to 2000 pmol/min did not cause vasodilatation but rather reduced forearm blood flow by Ϸ10% at the highest dose. A placebo-controlled study showed that angiotensin-(1-7) at 0.5 to 40 nmol/min caused weak but significant vasoconstriction (Pϭ0.0016 by ANOVA). Angiotensin-(1-7) at 100 pmol/min, but not at 10 pmol/min, significantly shifted the angiotensin II dose-response curve toward the right (meanϮSD of percent changes in forearm blood flow: Ϫ19Ϯ17%, Ϫ33Ϯ22%, Ϫ55Ϯ12%, Ϫ63Ϯ10%, and Ϫ68Ϯ5% at 5, 10, 25, 50, and 100 pmol/min of angiotensin II, respectively, with saline; 5Ϯ13%, 0.9Ϯ18%, Ϫ40Ϯ16%, Ϫ54Ϯ9%, and Ϫ61Ϯ6% with angiotensin-(1-7), Pϭ0.0021 by ANOVA). Angiotensin-(1-7) did not affect the dose-response curve of noradrenaline [3Ϯ12%, 5Ϯ16%, Ϫ20Ϯ22%, Ϫ31Ϯ18%, and Ϫ40Ϯ12% at 25, 50, 100, 300, and 600 pmol/min of noradrenaline, respectively, with saline; Ϫ4Ϯ15%, Ϫ2Ϯ23%, Ϫ29Ϯ22%, Ϫ34Ϯ16%, and Ϫ42Ϯ9% with angiotensin-(

Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

“…Because Ang III and Ang (1-7) did not cause vascular constriction in the adrenal arteries, their relaxing properties could counterbalance Ang II constrictions. Alternatively, high concentrations of Ang (1-7) infusion in humans reduced forearm blood flow 26 and in rats reduced blood flow to the kidney, mesentery, and skin. 27 The consequence of cortical artery Ang II metabolism on the concentrations of Ang II and Ang II metabolites that reach the adrenal steroidogenic cells depends on the steroidogenic activity of the metabolites.…”

Selective Angiotensin-Converting Enzyme C-Domain Inhibition Is Sufficient to Prevent Angiotensin I–Induced Vasoconstriction

“…1 However, it simultaneously reduced the maximum effect of Ang I, and identical observations were made toward Ang II. 19,20 This suggests that the Ang-(1-7) concentrations that selectively block the C-domain are also capable of blocking AT 1 receptors, thereby not allowing us to demonstrate the functional consequence of selective C-domain inhibition by Ang-(1-7) toward Ang I.…”

Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress

“…Angiotensin-converting enzyme inhibitor (ACEI) and AngⅡ type 2 receptor antagonist were effective in reducing the I/ R-induced injury (8). Since Ang-(1-7) opposed the physiological effects of AngⅡ, including its vasoconstrictive, proliferative and tropic effects (12,13), we hypothesized that Ang-(1-7) protects cardiomyocytes against I/ R-induced injury. Results of this study show that Ang-(1-7) was afforded cardioprotective effects against myocardial I/ R-induced damage, including attenuation of VA and cardiomyocyte apoptosis, as well as enhancement of LVSP.…”

“…In addition, Ang-(1-7) exhibits vasodilatory and antiproliferative activities in contrast to the constrictive and proliferative effects of AngⅡ. In human forearm resistant vessels, Ang-(1-7) has been shown to antagonize vasoconstriction by AngⅡ (12). One study also indicated that Ang-(1-7) inhibited the trophic actions of AngⅡ and reduced the expression of the mitogenic effects of normal serum and platelet-derived growth factor in the culture vascular smooth muscle cells (VSMCs), revealing the antiproliferative actions of Ang-(1-7) (13).…”