Angiotensin-(1-7) Augments Endothelium-dependent Relaxations of Porcine Coronary Arteries to Bradykinin by Inhibiting Angiotensin-Converting Enzyme 1
Angiotensin-(1-7) Augments Endothelium-dependent Relaxations of Porcine Coronary Arteries to Bradykinin by Inhibiting Angiotensin-Converting Enzyme 1
复制标题
DOI：
10.1097/fjc.0000000000000069
复制
发表时间：
2014-05-01
影响因子：
3
通讯作者：
Vanhoutte, Paul M.
中科院分区：
文献类型：
--
作者：
Raffai, Gabor;Khang, Gilson;Vanhoutte, Paul M.
Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin-(1-7) that activates Mas receptors, inhibits ACE1, and modulates bradykinin receptor sensitivity. This in vitro study compared the direct and indirect effects of angiotensin-(1-7), the ACE1 inhibitor captopril, and diminazene aceturate (DIZE) an alleged ACE2 activator in rings of porcine coronary arteries, by measuring changes of isometric tension. Angiotensin-(1-7), captopril, and DIZE did not cause significant changes in tension before or after desensitization of bradykinin receptors in preparations contracted with U46619. Bradykinin caused concentration-dependent and endothelium-dependent relaxations that were not affected by DIZE but were potentiated to a similar extent by angiotensin-(1-7) and captopril, given alone or in combination. Bradykinin responses potentiated by angiotensin-(1-7) and captopril were not affected by the BK1 antagonist SSR240612 and remained augmented in the presence of either N-omega-nitro-l-arginine methyl ester hydrochloride plus indomethacin or TRAM-34 plus UCL-1684. ACE2 was identified in the coronary endothelium by immunofluorescence, but its basal activity was not influenced by DIZE. These results suggest that in coronary arteries, angiotensin-(1-7) and captopril both improves NO bioavailability and enhances endothelium-dependent hyperpolarization to bradykinin solely by ACE1 inhibition. Endothelial ACE2 activity cannot be increased by DIZE to produce local adequate amounts of angiotensin-(1-7) to influence vascular tone.
