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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Ang(1-7) potentiates the vasodilating effect of bradykinin, possibly through a mechanism(s) involving nitric oxide release, in human forearm resistance vessels.
Ueda
S
S
Department of Medicine II, Yokohama City University School of Medicine, Yokohama 236-0004, Japan. sueda@med.yokohama-cu.ac.jp
Masumori-Maemoto
S
S
Wada
A
A
Ishii
M
M
Brosnihan
K B
KB
Umemura
S
S
D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin