RELEASE OF NITRIC BRIDE BY ANGIOTENSIN-(1-7) FROM PORCINE CORONARY ENDOTHELIUM - IMPLICATIONS FOR A NOVEL ANGIOTENSIN RECEPTOR

The angiotensin I (AI) metabolite, A(1-7), elicited a concentration-de pendent dilator response (ED(50) greater than or equal to 2 mu M) in p orcine coronary artery rings which was markedly attenuated by the nitr ic oxide (NO) synthase inhibitor, NG-nitro-L-arginine, and abolished a fter removal of the endothelium. This effect of the heptapeptide was n ot mimicked by AII, AIII or A(3-8) at comparable concentrations. The A (1-7)induced relaxation was not affected by AT(1) or AT(2) receptor bl ockade or cyclo-oxygenase inhibition, but was attenuated by the B-2 re ceptor antagonist, Hoe 140, and augmented by the angiotensin-convertin g enzyme (ACE) inhibitor, quinaprilat. These findings suggest that the relaxation to A(1-7) was mediated by the release of NO from the coron ary endothelium through activation of an, as yet unidentified, AT rece ptor, the occupation of which also seems to stimulate the release of v asoactive kinins. Since A(1-7) accumulates during ACE inhibition, this mechanism may contribute to the coronary dilator effect of ACE inhibi tors in vivo.