Abiru T, Watanabe Y, Kamata K, Kasuya Y
Biology Laboratory, Yamasa Corporation, Chiba, Japan.
Eur J Pharmacol. 1993 Sep 21;242(1):15-22. doi: 10.1016/0014-2999(93)90004-2.
We examined the relationship between relaxation responses of the mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 microM acetylcholine, 0.1 microM calcium ionophore A23187, and 1 microM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 microM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 microM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 microM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 microM methylene blue, and both the cAMP and cGMP levels were decreased. L-NG-Monomethyl arginine (L-NMMA) (100 microM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 microM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 microM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.
我们研究了肠系膜动脉床的舒张反应与大鼠肠系膜动脉床释放的环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）水平之间的关系。用1微摩尔/升乙酰胆碱、0.1微摩尔/升钙离子载体A23187和1微摩尔/升硝普钠灌注肠系膜制剂，均产生完全且持久的舒张，并增加流出液中cAMP以及cGMP的水平。在去内皮的制剂中，乙酰胆碱既不引起血管舒张，也不引起cAMP和cGMP水平升高。用1微摩尔/升硝普钠灌注去内皮制剂可引起完全舒张和cGMP水平显著升高，但不引起cAMP水平升高。异丙肾上腺素（1微摩尔/升）产生完全舒张并使cAMP水平升高，但对有内皮或无内皮的制剂中的cGMP水平均无影响。乙酰胆碱（0.001 - 1微摩尔/升）使制剂舒张，并使流出液中cAMP和cGMP水平呈剂量依赖性增加。用10微摩尔/升亚甲蓝灌注后，乙酰胆碱诱导的舒张反应逆转了45%，且cAMP和cGMP水平均降低。一氧化氮合酶抑制剂L - NG - 单甲基精氨酸（L - NMMA）（100微摩尔/升）完全逆转了0.1微摩尔/升乙酰胆碱诱导的舒张，并降低了升高的cGMP水平。吲哚美辛（1微摩尔/升）减少了乙酰胆碱诱导的cAMP释放，但未改变对乙酰胆碱的血管舒张反应。我们提出了一种同时测量大鼠肠系膜动脉床血管舒张以及释放的cAMP和cGMP水平变化的新方法。我们得出结论，该方法可能提供有关阻力血管内皮功能的信息。
