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 ≈10% 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 ( P =0.0016 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 (mean±SD of percent changes in forearm blood flow: −19±17%, −33±22%, −55±12%, −63±10%, and −68±5% at 5, 10, 25, 50, and 100 pmol/min of angiotensin II, respectively, with saline; 5±13%, 0.9±18%, −40±16%, −54±9%, and −61±6% with angiotensin-(1-7), P =0.0021 by ANOVA). Angiotensin-(1-7) did not affect the dose-response curve of noradrenaline [3±12%, 5±16%, −20±22%, −31±18%, and −40±12% at 25, 50, 100, 300, and 600 pmol/min of noradrenaline, respectively, with saline; −4±15%, −2±23%, −29±22%, −34±16%, and −42±9% with angiotensin-(1-7)]. Our results suggest that angiotensin-(1-7) antagonizes vasoconstriction by angiotensin II in human resistant vessels and might act as an endogenous angiotensin II antagonist.