Okamura T, Toda N
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Eur J Pharmacol. 1994 Apr 11;256(1):79-83. doi: 10.1016/0014-2999(94)90619-x.
The present study was aimed to determine the effect of calmodulin inhibitors on the relaxant response of isolated dog and monkey cerebral arteries to vasodilator nerve stimulation, which is hypothesized to be mediated by nitric oxide (NO) from nerve endings. The relaxations caused by nerve stimulation by electrical pulses in endothelium-denuded arteries were attenuated by treatment with calmidazolium and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride) and were abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, and tetrodotoxin. The calmodulin inhibitors also attenuated the relaxations caused by nicotine and substance P, which were endothelium-independent and -dependent, respectively, but did not influence the relaxant response to NO. It is concluded that calmodulin is required for activation of the NO synthase present in the vasodilator nerve as well as that in the endothelium.
本研究旨在确定钙调蛋白抑制剂对分离的犬和猴脑动脉对血管舒张神经刺激的舒张反应的影响，据推测这种反应是由神经末梢释放的一氧化氮（NO）介导的。在内皮剥脱的动脉中，电脉冲刺激神经引起的舒张反应，经氯氮卓和W-7（N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐）处理后减弱，而一氧化氮合酶抑制剂NG-硝基-L-精氨酸和河豚毒素则可消除这种反应。钙调蛋白抑制剂还减弱了分别由烟碱和P物质引起的舒张反应，烟碱引起的舒张反应不依赖内皮，P物质引起的舒张反应依赖内皮，但不影响对NO的舒张反应。结论是，钙调蛋白是激活血管舒张神经和内皮中存在的一氧化氮合酶所必需的。
