Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man

It has been clearly demonstrated that angiotensin(1-7) potentiates the vasodilating effect of bradykinin in isolated vessels of animals.

To investigate the interaction between angiotensin(1-7) Ang(1-7) and bradykinin in human forearm resistant vessels of normotensive healthy men in vivo, by the measurement of forearm blood flow using venous occlusion, strain-gauge plethysmography with intra-arterial infusions of peptides in a placebo-controlled, double-blind, cross-over design.

In eight men, bradykinin was infused intra-arterially twice; placebo, Ang(1-7), or angiotensin II was co-infused with the second infusion. The effect of inhibition of nitric oxide synthase on the interaction between Ang(1-7) and bradykinin was also tested in eight other individuals. The effects of Ang(1-7) were analyzed by analysis of variance (ANOVA) and by the ratios of individually derived areas under the dose-response curves (AUC) of bradykinin, adjusted for changes in the AUCs by repeated infusions of bradykinin with placebo.

Ang(1-7) (1000 pmol/min) significantly potentiated the vasodilating effect of bradykinin compared with the effect of saline (P = 0.0471, ANOVA) and in a dose-dependent manner (adjusted AUC ratio [95% confidence interval (CI)] 2.75 (1.72 to 3.78) with 1000 pmol/min, 1.62 (1.31 to 1.93) with 100 pmol/min, and 0.98 (0.80, to 1.09) with 10 pmol/min). This effect was completely abolished by co-infusion of NG-monomethyl-l-arginine [AUC ratio 0.98 (0.90 to 1.04)]. Ang(1-7) did not affect the vasodilating effects of either acetylcholine or sodium nitroprusside.

Ang(1-7) potentiates the vasodilating effect of bradykinin, possibly through a mechanism(s) involving nitric oxide release, in human forearm resistance vessels.