Schini V B, Vanhoutte P M
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
J Pharmacol Exp Ther. 1992 May;261(2):553-9.
The possibility that calmodulin inhibitors impair the constitutive but not the inducible nitric oxide synthase(s)-mediated inhibitions of tone was investigated in the rat aorta. The endothelium-dependent relaxations evoked by acetylcholine, ATP and the calcium ionophore A23187 (which are mediated by the constitutive nitric oxide synthase) were inhibited by calmodulin inhibitors [calmidazolium, W-7 and (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, hydrochloride, fendiline] and by an inhibitor of nitric oxide synthase, nitro L-arginine. Nitro L-arginine but not calmidazolium reduced the inhibitory influence of the endothelium on the concentration-contraction curves evoked by phenylephrine. Treatment of aortic rings without endothelium with interleukin-1 beta inhibited the contractions to phenylephrine by inducing nitric oxide synthase activity. Nitro L-arginine but not calmidazolium restored the contractility of the aortic rings. The relaxations evoked by a donor of nitric oxide, 3-morpholino-sydnonimine, were minimally affected by calmidazolium and nitro L-arginine. The basal tissue content in, and the production of, guanosine 3',5' cyclic monophosphate evoked by acetylcholine in rings with endothelium were inhibited by calmidazolium and nitro L-arginine. The production of cyclic GMP evoked by interleukin-1 beta in rings without endothelium was inhibited by nitro L-arginine but not by calmidazolium. These observations indicate that calmodulin inhibitors inhibit the constitutive but not the inducible nitric oxide synthase(s) in the rat aorta.
在大鼠主动脉中研究了钙调蛋白抑制剂损害组成型而非诱导型一氧化氮合酶介导的张力抑制作用的可能性。钙调蛋白抑制剂[氯米帕明、W - 7和（N -（6 - 氨基己基）- 5 - 氯 - 1 - 萘磺酰胺盐酸盐、芬地林]以及一氧化氮合酶抑制剂硝基 - L - 精氨酸可抑制由乙酰胆碱、ATP和钙离子载体A23187（由组成型一氧化氮合酶介导）引起的内皮依赖性舒张。硝基 - L - 精氨酸而非氯米帕明降低了内皮对去氧肾上腺素引起的浓度 - 收缩曲线的抑制作用。用白细胞介素 - 1β处理无内皮的主动脉环可通过诱导一氧化氮合酶活性抑制对去氧肾上腺素的收缩反应。硝基 - L - 精氨酸而非氯米帕明恢复了主动脉环的收缩性。一氧化氮供体3 - 吗啉代 - 西多胺引起的舒张反应受氯米帕明和硝基 - L - 精氨酸的影响极小。氯米帕明和硝基 - L - 精氨酸可抑制内皮环中乙酰胆碱引起的鸟苷3'，5' - 环磷酸的基础组织含量及其生成。硝基 - L - 精氨酸而非氯米帕明可抑制无内皮环中白细胞介素 - 1β引起的环磷酸鸟苷生成。这些观察结果表明，钙调蛋白抑制剂在大鼠主动脉中抑制组成型而非诱导型一氧化氮合酶。
