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
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.