ANGIOTENSIN-(1-7) AUGMENTS BRADYKININ-INDUCED VASODILATION BY COMPETING WITH ACE AND RELEASING NITRIC-OXIDE

Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with kinins and augments bradykinin (BK)-induced vasodilator response s by an unknown mechanism. In this study, we evaluated whether the pot entiation of the BK-induced vasodilation by Ang-(1-7) may be attributa ble to inhibition of BK metabolism, release of nitric oxide, or both. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers. I-125-[Tyr(0)]-BK metabolism was determin ed in vascular rings by assessing the degradation of the peptide by hi ghperformance liquid chromatography. Ang-(1-7) augmented the vasodilat ion induced by BK in a concentration-dependent manner in rings precons tricted with the thromboxane analog U46619. The EC(50) of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/- 0.08 nmol/L) was shifted leftward by 6.6- fold in the presence of 2 mu mol/L concentration of Ang-(1-7). The res ponse was specific for BK, since Ang-(1-7) did not augment the vasodil ation induced by either acetylcholine (0.05 mu mol/L) or sodium nitrop russide (0.1 mu mol/L). Moreover, neither angiotensin I nor angiotensi n II (Ang II) duplicated the augmented BK response of Ang-(1-7). Pretr eatment of vascular rings with the nitric oxide synthase inhibitor, N- omega-nitro-L-arginine (L-NA; 100 mu mol/L) completely abolished the e ffects of Ang-(1-7) on BK-induced vasodilation whereas pretreatment wi th indomethacin (10 mu mol/L) was without effect.