Endothelin-1-induced vasoconstriction does not require intracellular Ca²⁺ waves in arteries from rats exposed to intermittent hypoxia.
Endothelin-1-induced vasoconstriction does not require intracellular Ca²⁺ waves in arteries from rats exposed to intermittent hypoxia.
复制标题
内皮素-1诱导的血管收缩不需要暴露于间歇性缺氧的大鼠动脉中的细胞内Ca2+波。
DOI：
10.1152/ajpheart.00643.2013
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kanagy,NancyL
中科院分区：
文献类型：
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作者：
Osmond,JessicaM;GonzalezBosc,LauraV;Walker,BenjimenR;Kanagy,NancyL
睡眠呼吸暂停与心血管疾病有关，睡眠呼吸暂停患者血浆内皮素(ET)-1浓度升高。暴露于间歇性缺氧（IH）（一种睡眠呼吸暂停模型）的大鼠也会增加血浆ET-1浓度和肠系膜动脉对ET-1的收缩，而不会增加全局血管平滑肌细胞Ca2+浓度（[Ca2+]）。由于ET-1已被证明增加Ca2+波传播的发生，我们假设ET-1增加肠系膜动脉Ca2+波的活性，而不是全局[Ca2+]，以介导IH暴露后血管收缩增强。雄性Sprague-Dawley大鼠暴露于假或IH条件下，每天7小时，持续2周。假手术和ih暴露大鼠的肠系膜动脉被分离、插管并加压至75 mmHg，以测量et -1诱导的收缩以及全球[Ca2+]和Ca2+波活性的变化。低浓度的ET-1 （1 nM）在两组中引起类似的血管收缩和全局Ca2+反应。相反，ET-1对假手术大鼠动脉Ca2+波活性没有影响，但明显增加了ih暴露大鼠动脉Ca2+波频率。et -1诱导的IH大鼠动脉Ca2+波频率的增加依赖于磷脂酶C和肌醇1,4,5-三磷酸受体的激活，但抑制磷脂酶C和肌醇1,4,5-三磷酸受体并不能阻止et -1介导的血管收缩。这些结果表明，虽然ET-1在IH暴露后升高Ca2+波活性，但波活性的增加与血管收缩的增加无关。
Sleep apnea is associated with cardiovascular disease, and patients with sleep apnea have elevated plasma endothelin (ET)-1 concentrations. Rats exposed to intermittent hypoxia (IH), a model of sleep apnea, also have increased plasma ET-1 concentrations and heightened constriction to ET-1 in mesenteric arteries without an increase in global vascular smooth muscle cell Ca2+concentration ([Ca2+]). Because ET-1 has been shown to increase the occurrence of propagating Ca2+waves, we hypothesized that ET-1 increases Ca2+wave activity in mesenteric arteries, rather than global [Ca2+], to mediate enhanced vasoconstriction after IH exposure. Male Sprague-Dawley rats were exposed to sham or IH conditions for 7 h/day for 2 wk. Mesenteric arteries from sham- and IH-exposed rats were isolated, cannulated, and pressurized to 75 mmHg to measure ET-1-induced constriction as well as changes in global [Ca2+] and Ca2+wave activity. A low concentration of ET-1 (1 nM) elicited similar vasoconstriction and global Ca2+responses in the two groups. Conversely, ET-1 had no effect on Ca2+wave activity in arteries from sham rats but significantly increased wave frequency in arteries from IH-exposed rats. The ET-1-induced increase in Ca2+wave frequency in arteries from IH rats was dependent on phospholipase C and inositol 1,4,5-trisphosphate receptor activation, yet inhibition of phospholipase C and the inositol 1,4,5-trisphosphate receptor did not prevent ET-1-mediated vasoconstriction. These results suggest that although ET-1 elevates Ca2+wave activity after IH exposure, increases in wave activity are not associated with increased vasoconstriction.