Comparison of the effect of imidaprilat and ramiprilat on bronchoconstriction and hypotension induced by bradykinin in guinea pigs

Authors
Citation
H. Doi et H. Narita, Comparison of the effect of imidaprilat and ramiprilat on bronchoconstriction and hypotension induced by bradykinin in guinea pigs, INFLAMM RES, 49(10), 2000, pp. 506-512
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFLAMMATION RESEARCH
ISSN journal
1023-3830 → ACNP
Volume
49
Issue
10
Year of publication
2000
Pages
506 - 512
Database
ISI
SICI code
1023-3830(200010)49:10<506:COTEOI>2.0.ZU;2-W
Abstract
Objective: To demonstrate tissue selective bradykinin (BK) potentiating act ion of angiotensin converting enzyme inhibitors, we studied effects of imid aprilat and ramiprilat, active metabolites of imidapril and ramipril, respe ctively, on bronchoconstriction and hypotension both induced by BK in vasop ressin-infused anesthetized guinea pigs. Methods: We measured pulmonary inflation pressure and blood pressure in vas opressin-infused anesthetized guinea pigs at the same time. BK-induced chan ges in pulmonary inflation pressure and blood pressure before and after the administration of ACE inhibitor were compared. Results: Imidaprilat and ramiprilat enhanced BK-induced hypotension compara bly, and this effect was inhibited by N-omega-nitro-L-arginin-methylester ( L-NAME, a nitric oxide synthetase inhibitor). Although imidaprilat did not affect BK-induced bronchoconstriction, ramiprilat enhanced the bronchoconst riction significantly. SR48968, a selective NK2 receptor antagonist, signif icantly inhibited the enhancing effect of ramiprilat on BK-induced bronchoc onstriction. Conclusion: These results suggest that enhancement of BK-induced hypotensio n by imidaprilat and ramiprilat is mediated by nitric oxide (NO), but the m ediator of the enhancing action of ramiprilat on BK-induced bronchoconstric tion is mainly neurokinin A.