INHIBITION OF THE ANGIOTENSIN-CONVERTING ENZYME BY PERINDOPRILAT AND RELEASE OF NITRIC-OXIDE

被引：16

作者：

DESTA, B ^{[1
]}

VANHOUTTE, PM ^{[1
]}

BOULANGER, CM ^{[1
]}

机构：

[1] BAYLOR COLL MED,CTR EXPTL THERAPEUT,HOUSTON,TX 77030

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1995年 / 8卷 / 05期

关键词：

NITRIC OXIDE; CARBOXYPEPTIDASE; HOE-140; B-2; RECEPTORS; B-1;

D O I：

10.1016/0895-7061(95)00026-L

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Experiments were designed to investigate the mechanism underlying the endothelium-dependent relaxations to perindoprilat, a converting enzyme inhibitor, in canine coronary arteries previously exposed to bradykinin. Rings suspended in organ chambers were exposed to bradykinin for 3 min and washed extensively for 250 min. In rings previously exposed to the peptide, bradykinin induced relaxations which were augmented in the presence of perindoprilat; this response was not affected by indomethacin, but nitro-L-arginine induced a rightward shift of the relaxation to the pep;ide without affecting its maximal effect. In canine coronary arteries previously exposed to the peptide, perindoprilat caused endothelium-dependent relaxations (IC50 = 7.83), which had been observed previously at concentrations where the converting enzyme inhibitor did not augment the response to bradykinin. Carboxypeptidase B, but not aprotinin, impaired the relaxation to perindoprilat, suggesting a contribution of bradykinin. The relaxation to perindoprilat was not affected by the B-1 antagonist Leu(8)-des-Arg(9)-bradykinin. However, the bradykinin B-2 antagonist HOE-140 displayed a noncompetitive antagonism against the response to perindoprilat. The response to the converting enzyme inhibitor was not affected by indomethacin but was impaired significantly by nitro-L-arginine. The present findings suggest that in canine coronary arteries previously exposed to bradykinin, the relaxation to perindopriIat is mediated mainly by endothelium-derived nitric oxide. In addition, the response to perindopriIat may be due to factors other than just protection of bound bradykinin from degradation.

引用

页码：S1 / S6

页数：6

共 17 条

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