DeWitt B J, Cheng D Y, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Circ Res. 1994 Dec;75(6):1064-72. doi: 10.1161/01.res.75.6.1064.
Responses to des-Arg9-bradykinin, a selective kinin B1 receptor agonist, were characterized in the pulmonary vascular bed of the intact-chest cat. Injections of des-Arg9-bradykinin into the perfused lobar artery under low-resting tone conditions caused dose-related increases in lobar arterial pressure; whereas in the same experiment under elevated tone conditions, injections of the B1 agonist caused dose-related decreases in lobar arterial pressure. Vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions and vasodilator responses under elevated-tone conditions were antagonized by des-Arg9,[Leu8]-bradykinin, a kinin B1 receptor antagonist, whereas responses under low- and high-tone conditions were not altered by Hoe 140, a kinin B2 receptor antagonist. Vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions were attenuated by phentolamine, prazosin, and reserpine but not by sodium meclofenamate, suggesting that release of catecholamines and activation of alpha-adrenergic receptors are involved. Pulmonary vasodilator responses under elevated-tone conditions were inhibited by N omega-nitro-L-arginine methyl ester, suggesting that des-Arg9-bradykinin stimulates the release of nitric oxide, whereas meclofenamate and U-37883A, a nonsulfonylurea ATP-sensitive K+ channel antagonist, did not alter vasodilator responses to the B1 receptor agonist. These results suggest that vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions are mediated by the activation of kinin B1 receptors, the release of catecholamines within the lung, and the activation of alpha-adrenergic receptors, whereas vasodilator responses under elevated tone conditions are mediated by activation of B1 receptors and the release of nitric oxide from the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
在开胸猫的肺血管床中对选择性激肽B1受体激动剂去-精氨酸9-缓激肽的反应进行了表征。在低静息张力条件下，向灌注的叶动脉注射去-精氨酸9-缓激肽会导致叶动脉压力呈剂量相关增加；而在同一实验的高张力条件下，注射B1激动剂会导致叶动脉压力呈剂量相关降低。去-精氨酸9-缓激肽在低张力条件下的血管收缩反应以及在高张力条件下的血管舒张反应被激肽B1受体拮抗剂去-精氨酸9，[亮氨酸8]-缓激肽所拮抗，而在低张力和高张力条件下的反应不受激肽B2受体拮抗剂Hoe 140的影响。去-精氨酸9-缓激肽在低张力条件下的血管收缩反应被酚妥拉明、哌唑嗪和利血平减弱，但不受甲氯芬那酸钠影响，这表明儿茶酚胺的释放和α-肾上腺素能受体的激活参与其中。高张力条件下的肺血管舒张反应被Nω-硝基-L-精氨酸甲酯抑制，这表明去-精氨酸9-缓激肽刺激一氧化氮的释放，而甲氯芬那酸和非磺酰脲类ATP敏感性钾通道拮抗剂U-37883A并未改变对B1受体激动剂的血管舒张反应。这些结果表明，去-精氨酸9-缓激肽在低张力条件下的血管收缩反应是由激肽B1受体的激活、肺内儿茶酚胺的释放以及α-肾上腺素能受体的激活介导的，而高张力条件下的血管舒张反应是由B1受体的激活和内皮细胞一氧化氮的释放介导的。（摘要截短至250字）
