Captopril produces endothelium-dependent relaxation of dog isolated renal arteries. Potential role of bradykinin

B. Malomvolgyi, M. Z. Koltai, P. Hadhazy, G. Pogatsa, K. Magyar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effects of the angiotensin-converting enzyme inhibitors, captopril, lisinopril and enalapril-maleate (the latter being a prodrug that has to be converted into enalaprilat), and bradykinin were investigated in the presence or absence of indomethacin and bradykinin receptor antagonists in dog renal arterial rings precontracted with either prostaglandin F(2α) or phenylephrine. At a high precontraction level (10 μM of prostaglandin F(2α)), captopril did not relax the arteries. However, when the tension was low (0.5 μM), both captopril and lisinopril produced endothelium-dependent relaxations. The maximum relaxations for captopril and lisinopril were 57 ± 6% and 64 ± 15%, respectively. Enalapril-maleate failed to relax the renal arteries even when the vascular tone was low. In endothelium-intact arteries precontracted with phenylephrine (0.2 μM), captopril and lisinopril produced a maximum relaxation of 60 ± 9% and 29 ± 5%, respectively, in arteries with intact endothelium, whilst responses to enalapril-maleate were inconsistent. Renal artery rings with rubbed endothelium failed to relax in response to bradykinin or captopril. We observed significant variations in both captopril- and lisinopril-induced endothelium-dependent relaxations in one tenth of the preparations. The relaxations to bradykinin and captopril were not affected by indomethacin (3 μM), whereas they were markedly attenuated by N(G)-nitro-L-arginine (0.1 mM). The bradykinin-antagonist, Nα-adamantane-acetyl-D-Arg-(Hyp3, Thi5,8. D-Phe7)BK, or the specific bradykinin2 receptor antagonist, HOE140, completely abolished the relaxation responses to captopril and reduced the potency of bradykinin, but failed to affect the acetylcholine-induced responses. The results suggest that the relaxant effect of captopril is mediated by endogenous bradykinin or by activation of bradykinin receptors. The proposed mechanisms by which captopril relaxes the renal arteries are: (1) inhibition of tissue kininase II, which leads to accumulation of endogenous bradykinin; (2) shift in angiotensin I metabolism towards (a) relaxant angiotensin derivative(s); and (3) interaction with bradykinin receptors.

Original languageEnglish
Pages (from-to)39-52
Number of pages14
JournalArchives internationales de pharmacodynamie et de therapie
Volume330
Issue number1
Publication statusPublished - Dec 1 1995

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Captopril produces endothelium-dependent relaxation of dog isolated renal arteries. Potential role of bradykinin'. Together they form a unique fingerprint.

  • Cite this