Release of nitric oxide 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-dependent dilator response (ED50 > or = 2 microM) in porcine coronary artery rings which was markedly attenuated by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, and abolished after removal of the endothelium. This effect of the heptapeptide was not mimicked by AII, AIII or A(3-8) at comparable concentrations. The A(1-7)-induced relaxation was not affected by AT1 or AT2 receptor blockade or cyclo-oxygenase inhibition, but was attenuated by the B2 receptor antagonist, Hoe 140, and augmented by the angiotensin-converting enzyme (ACE) inhibitor, quinaprilat. These findings suggest that the relaxation to A(1-7) was mediated by the release of NO from the coronary endothelium through activation of an, as yet unidentified, AT receptor, the occupation of which also seems to stimulate the release of vasoactive kinins. Since A(1-7) accumulates during ACE inhibition, this mechanism may contribute to the coronary dilator effect of ACE inhibitors in vivo.
Centre of Physiology, Johann Wolfgang Goethe-University Clinic, Frankfurt/M., Germany.
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D000595:Amino Acid Sequence; D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000502:physiology*; D013552:Swine; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000494:pharmacology
D007546:Isoquinolines; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; C054501:quinaprilat; C065679:icatibant; D000803:Angiotensin I; D001120:Arginine; C118790:angiotensin I (1-7); D001920:Bradykinin