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-(

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

Our results suggest that angiotensin II may attenuate the arterial vasodilating effect of glyceryl trinitrate through angiotensin type 1 receptors and presumably through receptor-mediated superoxide production, which may be relevant to the development of nitrate tolerance.

P25 We investigated effects of subpressor dose of angiotensin II (ANG II) on the vasodilating effect of Glyceryl trinitrate (GTN)in 9 normotensive healthy males. GTN at 100, 250, 1000 ng/min was intra-arterially infused with ANG II at 1, 5 pmol/min or placebo (protocol 1) with noradrenaline (NA) at 50 pmol/min or placebo (protocol 2). Effect of intra-arterial infusion of vitamin C at 25 mg/min on the interaction between GTN and ANG II was also tested (protocol 3).Protocol 1 was repeated after single oral dose of angiotensin type 1 receptor blocker, Candesartan (8mg) or matched placebo (protocol 4). Forearm blood flow (FBF) was measured by strain gauge plethymograph. ANG II significantly and dose-dependently attenuated the vasodilating effect of GTN (means±S.D. of % changes of FBF: 28±8, 79±22, 208±28 % at 100, 250, 1000 pmol/min of GTN with placebo, 8±6, 47±13, 173±31 with ANG II 1 pmol/min, 2±10, 39±13, 132±23 with ANG II 5 pmol/min. P=0.0057 vs placebo by ANOVA).NA did not affect the vasodilating effect of GTN. Co-infusion of vitamin C (25 mg/min)completely abolished the the interaction between ANG II and GTN. Attenuation of the effect of GTN by ANG II disappeared after the single dose of Candesartan. In summary, subpressor dose of ANG II attenuated the effect of GTN. There was a lack of effect of ANG II in the presence of either vitamin C or Candesartan. Our results suggest that ANG II may stimulate superoxide production through AT1 receptor which inactivates NO by forming peroxynitrite.