Santiago J A, Garrison E A, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1994 Aug;267(2 Pt 2):H828-36. doi: 10.1152/ajpheart.1994.267.2.H828.
The mechanisms and receptor subtype mediating vasodilator responses to bradykinin were investigated in the hindquarters vascular bed of the cat under constant flow conditions. Intraarterial injections of bradykinin in doses of 10-1,000 ng into the hindquarters vascular bed caused dose-related decreases in perfusion pressure that were inhibited by Hoe-140, a bradykinin B2-receptor antagonist. Injections of des-Arg9-bradykinin (in doses 10-fold higher than for bradykinin) caused smaller dose-related decreases in hindquarters perfusion pressure that were not blocked by Hoe-140. Administration of atropine, glibenclamide, or cyclooxygenase inhibitors did not alter vasodilator responses to bradykinin, suggesting that activation of muscarinic receptors, ATP-sensitive K+ channels, or prostaglandin release is not involved in the response to the peptide. Administration of N omega-nitro-L-arginine and its methyl ester reduced vasodilator responses to bradykinin, acetylcholine, and substance P, whereas responses to endothelium-independent vasodilator agents were not attenuated. Decreases in systemic arterial pressure and in hindquarters perfusion pressure in response to bradykinin were enhanced by the angiotensin-converting enzyme inhibitors captopril and enalaprilat. These results suggest that hindquarters vasodilator responses to bradykinin are mediated by activation of kinin B2 receptors and in part by the release of nitric oxide. These data also suggest the presence of bradykinin B1 receptors, mediating vasodilation in the hindquarters vascular bed. These results indicate that bradykinin is rapidly inactivated by angiotensin-converting enzyme in the lung and in the hindquarters vascular bed of the cat.
在猫后肢血管床恒定血流条件下，研究了介导缓激肽血管舒张反应的机制和受体亚型。向后肢血管床动脉内注射剂量为10 - 1000 ng的缓激肽，可引起灌注压呈剂量相关下降，该下降被缓激肽B2受体拮抗剂Hoe - 140抑制。注射去精氨酸9 - 缓激肽（剂量比缓激肽高10倍）引起后肢灌注压较小的剂量相关下降，且未被Hoe - 140阻断。给予阿托品、格列本脲或环氧化酶抑制剂并未改变对缓激肽的血管舒张反应，表明毒蕈碱受体、ATP敏感性钾通道的激活或前列腺素释放不参与对该肽的反应。给予Nω-硝基-L-精氨酸及其甲酯可降低对缓激肽、乙酰胆碱和P物质的血管舒张反应，而对不依赖内皮的血管舒张剂的反应未减弱。血管紧张素转换酶抑制剂卡托普利和依那普利拉增强了缓激肽引起的全身动脉压和后肢灌注压下降。这些结果表明，后肢对缓激肽的血管舒张反应由激肽B2受体激活介导，部分由一氧化氮释放介导。这些数据还提示存在缓激肽B1受体，介导后肢血管床的血管舒张。这些结果表明，缓激肽在猫的肺和后肢血管床中被血管紧张素转换酶迅速灭活。
