Angiotensin-(1-7) attenuates vasoconstriction evoked by angiotensin II but not by noradrenaline in man.
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 approximately 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.
Ueda
S
S
Department of Medicine II, Yokohama City University School of Medicine, Yokohama, Japan. sueda@med.yokohama-cu.ac.jp
Masumori-Maemoto
S
S
Ashino
K
K
Nagahara
T
T
Gotoh
E
E
Umemura
S
S
Ishii
M
M
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D009638:Norepinephrine