Pörsti I, Bara A T, Busse R, Hecker M
Centre of Physiology, Johann Wolfgang Goethe-University Clinic, Frankfurt/M., Germany.
Br J Pharmacol. 1994 Mar;111(3):652-4. doi: 10.1111/j.1476-5381.1994.tb14787.x.
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.
血管紧张素I（AI）的代谢产物A（1-7）可引起猪冠状动脉环浓度依赖性的舒张反应（半数有效剂量≥2微摩尔），一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸可显著减弱该反应，去除内皮后反应消失。在可比浓度下，八肽血管紧张素II、血管紧张素III或A（3-8）不能模拟七肽的这种作用。A（1-7）诱导的舒张不受AT1或AT2受体阻断或环氧化酶抑制的影响，但可被B2受体拮抗剂Hoe 140减弱，并被血管紧张素转换酶（ACE）抑制剂喹那普利拉增强。这些发现表明，A（1-7）的舒张作用是通过激活一种尚未明确的AT受体，使冠状动脉内皮释放NO介导的，该受体的占据似乎还能刺激血管活性激肽的释放。由于A（1-7）在ACE抑制过程中会蓄积，这一机制可能有助于ACE抑制剂在体内产生冠状动脉舒张作用。
