Oxygen modulates alpha 1B-adrenergic receptor gene expression by arterial but not venous vascular smooth muscle.
Oxygen modulates alpha 1B-adrenergic receptor gene expression by arterial but not venous vascular smooth muscle.
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氧气通过动脉而非静脉血管平滑肌调节 α1B-肾上腺素能受体基因表达。
DOI：
10.1152/ajpheart.1996.271.4.h1599
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Faber,JE
中科院分区：
文献类型：
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作者：
Eckhart,AD;Zhu,Z;Arendshorst,WJ;Faber,JE
血液和组织O2水平是血管平滑肌细胞(SMC)张力短期自我调节调节的主要决定因素，并可能影响SMC儿茶酚胺反应性的长期变化。我们验证了长时间低氧改变α1肾上腺素受体基因表达的假说。体外培养的主动脉SMC在3%O2中孵育8h后，α1B基因表达增加，分别为对照组细胞(21%O2)的523%(P=0.02)和器官培养的SMC的205%(P=0.04)。在体内，低氧(10%吸氧)同样使主动脉SMCα1B基因表达增加180%(P=0.02)。相反，在体外、在体和在体模型中，低氧对主动脉SMCα1D、α-肌动蛋白和β-肌动蛋白的mRNA水平无明显影响。与主动脉SMC不同，下腔静脉SMCα1B、α1D、α-肌动蛋白和β-肌动蛋白mRNA的表达不随低氧暴露而变化。主动脉SMCα1B转录水平增加360%(P=0.02)，而α1D、α-肌动蛋白和β-肌动蛋白转录水平无明显变化。低氧暴露对α1B和α1D基因的稳定性均无影响。3%O2作用24 h后，α1肾上腺素受体总密度([~3H]哌唑嗪结合量)增加12%(P=0.04)。这与氯乙基可乐定(CEC)敏感的α1肾上腺素受体数量增加200%(P<；0.01)有关，而CEC不敏感的α1肾上腺素受体密度没有变化。用Fura 2测定，动脉SMC暴露于3%O2的24 h可增加去甲肾上腺素引起的细胞内钙升高的最大反应。低O2不改变对另一种G蛋白偶联受体血管紧张素II的反应。这些数据表明，在长期低氧或组织缺血期间，低O2可能选择性地增加动脉血管中功能偶联的α1B肾上腺素受体的表达。
Blood and tissue O2 levels are major determinants of short-term autoregulatory adjustments in vascular smooth muscle cell (SMC) tension and may effect long-term alterations in SMC catecholamine responsiveness. We examined the hypothesis that prolonged hypoxia altered gene expression of alpha 1-adrenoceptors. After exposure of cultured aortic (in vitro) SMC to 3% O2 for 8 h, alpha 1B mRNA increased to 523% (P = 0.02) of control cells (21% O2) and to 205% (P = 0.04) in in situ organ-cultured aortic SMC. In vivo hypoxic hypoxia (10% inspired O2) similarly increased aortic SMC alpha 1B mRNA 180% (P = 0.02). In contrast, alpha 1D, alpha-actin and beta-actin mRNA levels were not changed in aortic SMC by low O2 in the in vitro, in situ, or in vivo models. Unlike aortic SMC, vena caval SMC alpha 1B mRNA expression did not change with low-O2 exposure in vitro or in vivo, nor did alpha 1D, alpha-actin or beta-actin mRNA. Aortic SMC alpha 1B transcription rate increased 360% (P = 0.02), whereas alpha 1D, alpha-actin, and beta-actin transcription was unchanged. Neither alpha 1B nor alpha 1D mRNA stability was altered by low-O2 exposure. Total alpha 1-adrenoceptor density ([3H]prazosin binding) increased 12% (P = 0.04) after 24 h of 3% O2. This was associated with a 200% increase (P < 0.01) in the chloroethylclonidine (CEC)-sensitive alpha 1-adrenoceptor population and no change in CEC-insensitive alpha 1-adrenoceptor density. Exposure of aortic SMC to 24 h of 3% O2 increased the maximum response of norepinephrine-evoked elevations in intracellular Ca2+ as measured using fura 2. Low O2 did not change responses to another G protein-coupled receptor, angiotensin II. These data suggest that reduced O2, during prolonged hypoxemia or tissue ischemia, may selectively increase expression of functionally coupled alpha 1B-adrenoceptors in arterial blood vessels.