Ignarro L J, Byrns R E, Buga G M, Wood K S
Department of Pharmacology, University of California School of Medicine, Los Angeles 90024.
Am J Physiol. 1987 Nov;253(5 Pt 2):H1074-82. doi: 10.1152/ajpheart.1987.253.5.H1074.
The objective of this study was to elucidate the mechanisms by which bradykinin and vasoactive intestinal polypeptide (VIP) relax bovine intrapulmonary artery and bradykinin, but not VIP, relaxes intrapulmonary vein. Bradykinin and VIP elicited entirely endothelium-dependent relaxation of phenylephrine-precontracted arterial rings, and this was associated with arterial accumulation of both guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). Bradykinin, but not VIP, relaxed precontracted venous rings and increased cGMP, but not cAMP levels, by endothelium-dependent mechanisms. Neither arteries nor veins relaxed in response to substance P, thrombin, bombesin, arginine vasopressin, or angiotensin II. Methylene blue or indomethacin each partially antagonized, whereas both, when together, abolished arterial relaxant responses to bradykinin and VIP. Methylene blue or indomethacin, respectively, abolished arterial cGMP or cAMP accumulation elicited by bradykinin and VIP. Venous relaxation and cGMP accumulation elicited by bradykinin was abolished by methylene blue but was unaltered by indomethacin. Thus bradykinin and VIP relaxed bovine intrapulmonary artery by endothelium-dependent mechanisms involving the actions of cGMP and cAMP whose formation may be stimulated by endothelium-derived relaxing factor and prostacyclin, respectively. In contrast, bradykinin relaxed intrapulmonary vein by endothelium-dependent mechanisms involving only cGMP.
本研究的目的是阐明缓激肽和血管活性肠肽（VIP）使牛肺内动脉舒张以及缓激肽（而非VIP）使肺内静脉舒张的机制。缓激肽和VIP引起苯肾上腺素预收缩的动脉环完全依赖内皮的舒张，这与鸟苷3',5'-环磷酸（cGMP）和腺苷3',5'-环磷酸（cAMP）在动脉中的蓄积有关。缓激肽而非VIP通过依赖内皮的机制使预收缩的静脉环舒张并增加cGMP水平，但不增加cAMP水平。动脉和静脉对P物质、凝血酶、蛙皮素、精氨酸加压素或血管紧张素II均无舒张反应。亚甲蓝或吲哚美辛各自部分拮抗，而两者同时使用时则消除了动脉对缓激肽和VIP的舒张反应。亚甲蓝或吲哚美辛分别消除了缓激肽和VIP引起的动脉cGMP或cAMP蓄积。缓激肽引起的静脉舒张和cGMP蓄积被亚甲蓝消除，但不受吲哚美辛影响。因此，缓激肽和VIP通过依赖内皮的机制使牛肺内动脉舒张，该机制涉及cGMP和cAMP的作用，其形成可能分别由内皮源性舒张因子和前列环素刺激。相比之下，缓激肽通过仅涉及cGMP的依赖内皮的机制使肺内静脉舒张。
