Doi H, Narita H
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
Inflamm Res. 2000 Oct;49(10):506-12. doi: 10.1007/s000110050623.
To demonstrate tissue selective brady-kinin (BK) potentiating action of angiotensin converting enzyme inhibitors, we studied effects of imidaprilat and ramiprilat, active metabolites of imidapril and ramipril, respectively, on bronchoconstriction and hypotension both induced by BK in vasopressin-infused anesthetized guinea pigs.
We measured pulmonary inflation pressure and blood pressure in vasopressin-infused anesthetized guinea pigs at the same time. BK-induced changes in pulmonary inflation pressure and blood pressure before and after the administration of ACE inhibitor were compared.
Imidaprilat and ramiprilat enhanced BK-induced hypotension comparably, and this effect was inhibited by Nomega-nitro-L-arginin-methylester (L-NAME, a nitric oxide synthetase inhibitor). Although imidaprilat did not affect BK-induced bronchoconstriction, ramiprilat enhanced the broncho-constriction significantly. SR48968, a selective NK2 receptor antagonist, significantly inhibited the enhancing effect of ramiprilat on BK-induced bronchoconstriction.
These results suggest that enhancement of BK-induced hypotension by imidaprilat and ramiprilat is mediated by nitric oxide (NO), but the mediator of the enhancing action of ramiprilat on BK-induced bronchoconstriction is mainly neurokinin A.
为了证明血管紧张素转换酶抑制剂对组织具有选择性缓激肽（BK）增强作用，我们分别研究了咪达普利拉和雷米普利拉（分别是咪达普利和雷米普利的活性代谢产物）对血管加压素输注麻醉豚鼠中BK诱导的支气管收缩和低血压的影响。
我们同时测量了血管加压素输注麻醉豚鼠的肺充气压力和血压。比较了给予血管紧张素转换酶抑制剂前后BK诱导的肺充气压力和血压变化。
咪达普利拉和雷米普利拉同等程度地增强了BK诱导的低血压，并且这种作用被N-硝基-L-精氨酸甲酯（L-NAME，一种一氧化氮合酶抑制剂）抑制。虽然咪达普利拉不影响BK诱导的支气管收缩，但雷米普利拉显著增强了支气管收缩。选择性NK2受体拮抗剂SR48968显著抑制了雷米普利拉对BK诱导的支气管收缩的增强作用。
这些结果表明，咪达普利拉和雷米普利拉对BK诱导的低血压的增强作用是由一氧化氮（NO）介导的，但雷米普利拉对BK诱导的支气管收缩的增强作用的介质主要是神经激肽A。
