Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cGMP
Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cGMP
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DOI：
10.1152/ajpheart.1997.272.6.h2765
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发表时间：
1997-06-01
影响因子：
4.8
通讯作者：
White, RE
中科院分区：
文献类型：
--
作者：
Darkow, DJ;Lu, L;White, RE
雌激素被认为对心血管疾病有保护作用，现在有证据表明这种保护作用涉及直接的血管舒张作用。我们之前已经证明，雌激素通过鸟苷3 '，5'-环磷酸（cGMP）依赖性磷酸化打开肌细胞的大电导钙和电压激活钾（BKCa）通道，从而松弛内皮剥脱的猪冠状动脉（35）。目前的研究证实了这些结果，现在表明，这一机制涉及一氧化氮（NO）的生产。S-亚硝基-N-乙酰青霉胺（SNAP），NO供体，或8-溴-cGMP模拟雌激素对BKCa通道的作用。此外，抑制一氧化氮合酶（NOS）衰减雌激素或他莫昔芬诱导的BKCa-通道活性，这种作用被解除L-精氨酸。鸟苷酸环化酶活性的抑制阻断了雌激素、SNAP或L-精氨酸对BKc通道的刺激作用。此外，17 β-雌二醇刺激冠状动脉心肌细胞中亚硝酸盐和cGMP的积累。因此，我们建议雌激素对冠状动脉循环的血管舒张作用是由NO介导的。雌激素的有益心血管作用的一部分可能归因于血管平滑肌的舒张过程，涉及NO和cGMP依赖性刺激BKCa通道。
Estrogens are proposed to exert protection against cardiovascular disease, and evidence now suggests that this protection involves a direct vasodilatory effect. We have shown previously that estrogen relaxes endothelium-denuded porcine coronary arteries by opening the large-conductance calcium- and voltage-activated potassium (BKCa) channel of myocytes through guanosine 3',5'-cyclic monophosphate (cGMP)-dependent phosphorylation (35). The present study confirms these results and now demonstrates that this mechanism involves production of nitric oxide (NO). S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or 8-bromo-cGMP mimicked the effect of estrogen on BKCa channels. Furthermore, inhibition of NO synthase (NOS) attenuated estrogen- or tamoxifen-induced BKCa-channel activity, and this effect was disinhibited by L-arginine. Inhibition of guanylyl cyclase activity blocked the stimulatory effect of estrogen, SNAP, or L-arginine on BKc, channels. Furthermore, 17 beta-estradiol stimulated accumulation of nitrite and cGMP in coronary myocytes. Therefore, we propose that the vasodilatory effect of estrogen on the coronary circulation is mediated by NO. A portion of the beneficial cardiovascular effects of estrogen may be attributed to relaxation of vascular smooth muscle by a process that involves NO- and cGMP-dependent stimulation of BKCa channels.