48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization
48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization
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DOI：
10.1152/ajpregu.00104.2002
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发表时间：
2002-07-01
影响因子：
2.8
通讯作者：
Walker, BR
中科院分区：
文献类型：
--
作者：
Earley, S;Naik, JS;Walker, BR
慢性缺氧（CH）导致清醒大鼠对血管收缩剂的敏感性降低，并在恢复正常氧后持续存在。我们假设，这种效果是由于内皮依赖性超极化的血管平滑肌（VSM）细胞后CH。VSM细胞静息膜电位测定上级肠系膜动脉条CH大鼠（PB = 380托48小时）和常氧对照。与对照组相比，常氧下研究的CH大鼠VSM细胞超极化。与对照组相比，从CH大鼠分离的血管中静息血管壁细胞内Ca 2+浓度（[Ca 2 +]（i））和压力诱导的血管收缩减少。在CH大鼠的阻力动脉中，α（1）-肾上腺素能激动剂苯肾上腺素（PE）引起的血管收缩和血管壁[Ca 2 +]（i）增加也被钝化。去除内皮使静息膜电位、静息血管壁[Ca 2 +]（i）、压力诱导的血管收缩反应以及组间PE诱导的收缩反应和Ca 2+反应正常化。而VSM细胞超极化持续存在的一氧化氮合酶抑制，血红素加氧酶抑制恢复VSM细胞静息膜电位从CH大鼠血管到对照水平。我们的结论是，内皮源性CO占持续VSM细胞超极化和血管收缩反应低下后CH。
Chronic hypoxia (CH) results in reduced sensitivity to vasoconstrictors in conscious rats that persists upon restoration of normoxia. We hypothesized that this effect is due to endothelium-dependent hyperpolarization of vascular smooth muscle (VSM) cells after CH. VSM cell resting membrane potential was determined for superior mesenteric artery strips isolated from CH rats (PB = 380 Torr for 48 h) and normoxic controls. VSM cells from CH rats studied under normoxia were hyperpolarized compared with controls. Resting vessel wall intracellular Ca2+ concentration ([Ca2+](i)) and pressure-induced vasoconstriction were reduced in vessels isolated from CH rats compared with controls. Vasoconstriction and increases in vessel wall [Ca2+](i) in response to the alpha(1)-adrenergic agonist phenylephrine (PE) were also blunted in resistance arteries from CH rats. Removal of the endothelium normalized resting membrane potential, resting vessel wall [Ca2+](i), pressure-induced vasoconstrictor responses, and PE-induced constrictor and Ca2+ responses between groups. Whereas VSM cell hyperpolarization persisted in the presence of nitric oxide synthase inhibition, heme oxygenase inhibition restored VSM cell resting membrane potential in vessels from CH rats to control levels. We conclude that endothelial derived CO accounts for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity after CH.