Lamontagne D, Nakhostine N, Couture R, Nadeau R
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
J Cardiovasc Pharmacol. 1996 Nov;28(5):645-50. doi: 10.1097/00005344-199611000-00006.
Our study was performed to investigate the mechanism underlying the phypotensive effect of kinin B1-receptor activation with des-Arg9-bradykinin (des-Arg9-BK), in comparison with B2-receptor activation with bradykinin (BK), in anesthetized dogs. Bolus intravenous and intraarterial injections of both kinins were compared. BK (0.6 microgram/kg) produced a transient hypotension of the same magnitude, regardless of the route of administration (from 110 +/- 6 mm Hg to 66 +/- 6 mm Hg, or -41 +/- 5%). In contrast, intraarterial injection of des-Arg9-BK (0.6 microgram/kg) induced a weaker hypotension compared with its intravenous injection (-27 +/- 2% vs. -39 +/- 3%, p < 0.05). The hypotension induced by both kinins was accompanied by increases in heart rate, maximum left ventricular dP/dt, and aortic blood flow, suggesting a reduction in peripheral resistance. The positive inotropic and chronotropic effects of BK and des-Arg9-BK were found to be mediated by the sympathetic nervous system, because they were abolished by propranolol. The hypotension induced by intravenous and intraarterial injections of BK and intravenous injections of des-Arg9-BK was only slightly reduced after nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (L-NNA). In contrast, the hypotensive effect of intraarterial injection of des-Arg9-BK was reduced by half after treatment with L-NNA (p < 0.05). Neither bilateral vagotomy nor ganglionic blockade with pentolinium reduced the hypotension induced by both kinins. In conclusion, the hypotensive effect of des-Arg9-BK and BK results from a peripheral vasodilation. The contribution of NO in this vasodilation is substantial for des-Arg9-BK when administered intraarterial but limited for BK and intravenous des-Arg9-BK.
我们进行这项研究的目的是，在麻醉犬中，与缓激肽（BK）激活B2受体相比较，研究去-精氨酸9-缓激肽（des-Arg9-BK）激活激肽B1受体产生降压作用的潜在机制。对两种激肽进行了静脉推注和动脉内注射并比较。无论给药途径如何，BK（0.6微克/千克）均产生相同程度的短暂性低血压（从110±6毫米汞柱降至66±6毫米汞柱，即-41±5%）。相比之下，动脉内注射des-Arg9-BK（0.6微克/千克）与静脉注射相比，诱导的低血压较弱（-27±2%对-39±3%，p<0.05）。两种激肽诱导的低血压均伴有心率、左心室最大dP/dt和主动脉血流量增加，提示外周阻力降低。发现BK和des-Arg9-BK的正性肌力和变时作用由交感神经系统介导，因为它们被普萘洛尔消除。用NG-硝基-L-精氨酸（L-NNA）抑制一氧化氮（NO）合酶后，静脉和动脉内注射BK以及静脉注射des-Arg9-BK诱导的低血压仅略有降低。相比之下，用L-NNA治疗后，动脉内注射des-Arg9-BK的降压作用降低了一半（p<0.05）。双侧迷走神经切断术或用潘托铵进行神经节阻断均未降低两种激肽诱导的低血压。总之，des-Arg9-BK和BK的降压作用源于外周血管舒张。当动脉内给药时，NO在这种血管舒张中对des-Arg9-BK的作用很大，但对BK和静脉注射的des-Arg9-BK作用有限。
