Modulation of endothelium-dependent hyperpolarization and relaxation to acetylcholine in rat mesenteric artery by cytochrome P450 enzyme activity
Modulation of endothelium-dependent hyperpolarization and relaxation to acetylcholine in rat mesenteric artery by cytochrome P450 enzyme activity
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DOI：
10.1161/01.res.79.4.827
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发表时间：
1996-10-01
影响因子：
20.1
通讯作者：
Cheung, DW
中科院分区：
文献类型：
--
作者：
Chen, GF;Cheung, DW
同步微电极和张力记录的研究表明，乙酰胆碱（ACh）可诱导去甲肾上腺素收缩的大鼠肠系膜动脉的超极化和舒张。我们测试了是否超极化乙酰胆碱的细胞色素P450酶的诱导和耗竭修改。用3-甲基胆蒽和β-萘酮处理动物3天的酶诱导导致内皮依赖性超极化显著增加，从未处理动物动脉中的13.9+/-0.4 mV增加至最大值22.7+/-1.0 mV。通过用CoCl 2处理动物2天进行酶耗竭，导致最大超极化显著降低至9.9+/-0.7 mV。当NO合成被N-ω-硝基-L-精氨酸抑制时，舒张与超极化相关。克霉唑显著抑制N-ω-硝基-L-精氨酸抗性反应。乙酰胆碱的松弛没有改变酶诱导，但显着减少酶耗竭。在KCl收缩的动脉中，细胞色素P450酶活性的改变对ACh的舒张没有显著影响。同样，超极化和松弛吡那地尔没有显着影响。这些结果表明，ACh的超极化反应是密切调节细胞色素P450依赖酶。
Acetylcholine (ACh) induced hyperpolarization and relaxation in rat mesenteric arteries contracted with norepinephrine, as indicated from studies with simultaneous microelectrode and tension recordings. We tested whether the hyperpolarization to ACh was modified by induction and depletion of cytochrome P450 enzymes. Enzyme induction by treating the animals with 3-methylcholanthrene and beta-naphthoflavone for 3 days resulted in a significant increase in the endothelium-dependent hyperpolarization to a maximum of 22.7+/-1.0 mV from 13.9+/-0.4 mV in arteries from untreated animals. Enzyme depletion by treating the animals with CoCl2 for 2 days resulted in a significant reduction in the maximum hyperpolarization to 9.9+/-0.7 mV. When NO synthesis was inhibited by N-omega-nitro-L-arginine, the relaxation was correlated to hyperpolarization. The N-omega-nitro-L-arginine-resistant responses were significantly inhibited by clotrimazole. The relaxation to ACh was not altered by enzyme induction but was significantly reduced by enzyme depletion. In KCl-contracted arteries, modification of cytochrome P450 enzyme activity had no significant effect on the relaxation to ACh. Similarly, hyperpolarization and relaxation to pinacidil were not significantly affected. These results suggest that the hyperpolarization response to ACh is closely regulated by cytochrome P450-dependent enzymes.