Departments of Medicine and Physiology & Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, and Vascular Biology Research Group, Robarts Research Institute, 100 Perth Drive, PO Box 5015, Stn B, London, ON, Canada.
Hypertension. 2011 Mar;57(3):442-51. doi: 10.1161/HYPERTENSIONAHA.110.161653. Epub 2011 Jan 17.
It has been increasingly appreciated that steroids elicit acute vascular effects through rapid, so-called nongenomic signaling pathways. Though aldosterone, for example, has been demonstrated to mediate rapid vascular effects via both mineralocorticoid receptor-dependent and -independent pathways, the mechanism(s) of this mineralocorticoid receptor-independent effect of aldosterone is yet to be determined. For estrogen, its rapid effects have been reported to be, at least in part, mediated via the 7-transmembrane-spanning, G protein-coupled receptor GPR30. Previous studies have demonstrated common response outcomes in response to both aldosterone and estrogen on GPR30 expression, ie, activation of phosphatidylinositol 3-kinase-dependent contraction and extracellular signal-regulated kinase activation in vascular smooth muscle cells. The present studies were undertaken to test the hypothesis that the rapid response to aldosterone in smooth muscle is dependent on the availability of a GPR30-dependent signaling pathway. These findings not only reconcile differences in the literature for aldosterone response in freshly isolated versus cultured aortic smooth muscle cells but also suggest alternative therapeutic strategies for modulating aldosterone actions on the vasculature in vivo.
人们越来越认识到，类固醇通过快速的、所谓的非基因组信号通路引起急性血管效应。例如，醛固酮已被证明通过盐皮质激素受体依赖性和非依赖性途径介导快速的血管效应，但醛固酮的这种盐皮质激素受体非依赖性效应的机制尚待确定。对于雌激素，其快速作用至少部分是通过 7 跨膜转导、G 蛋白偶联受体 GPR30 介导的。先前的研究表明，对 GPR30 表达，醛固酮和雌激素的共同反应结果，即血管平滑肌细胞中磷酸肌醇 3-激酶依赖性收缩和细胞外信号调节激酶激活的激活。本研究旨在验证以下假设：即平滑肌对醛固酮的快速反应依赖于 GPR30 依赖性信号通路的可用性。这些发现不仅调和了文献中关于新鲜分离和培养的主动脉平滑肌细胞中醛固酮反应的差异，而且还为体内调节醛固酮对血管的作用提供了替代的治疗策略。
