Feldman Ross D, Gros Robert
Cell Signaling and Vascular Biology Research Groups, Robarts Research Institute, London, Ontario, Canada.
Curr Opin Nephrol Hypertens. 2006 Mar;15(2):135-40. doi: 10.1097/01.mnh.0000214772.96361.ef.
The purpose of this article is to review recent evidence relating to the regulation of vasodilatation and alterations in these mechanisms in the hypertensive state. In particular, we will focus on signaling systems regulating nitric oxide synthase and intracellular cyclic AMP - the two principal mechanisms mediating vasodilatation.
G-protein-coupled-receptor-mediated, endothelial-dependent processes are increasingly being seen as critical vasodilatory mechanisms. Impairment of endothelial responses to G-protein-coupled receptor activation is a key component of the decrease in G-protein-coupled-receptor-mediated vasodilatation in hypertension. In addition, an 'uncoupling' of the G-protein-coupled receptor/G-protein complex is the principal mechanism underlying impaired G-protein-coupled-receptor-mediated vasodilatation in hypertension. Alterations in G-protein-coupled receptor kinase function have a central role underlying this defect. Finally, the importance of the expression of genetic variants of G-protein-coupled receptors and G-proteins underlying the defect in vasodilatation in hypertension remains contentious.
G-protein signaling pathways in the vasculature play an important role in both the development and the maintenance of the hypertensive state. It is unlikely, however, that any single defect in the G-protein-linked vasodilatory pathway will ever be shown to be the sole cause of hypertension.
本文旨在综述近期有关血管舒张调节及高血压状态下这些机制改变的证据。特别地，我们将聚焦于调节一氧化氮合酶和细胞内环磷酸腺苷的信号系统——介导血管舒张的两个主要机制。
G蛋白偶联受体介导的内皮依赖性过程日益被视为关键的血管舒张机制。内皮对G蛋白偶联受体激活的反应受损是高血压中G蛋白偶联受体介导的血管舒张减少的关键组成部分。此外，G蛋白偶联受体/G蛋白复合物的“解偶联”是高血压中G蛋白偶联受体介导的血管舒张受损的主要机制。G蛋白偶联受体激酶功能的改变在这一缺陷中起核心作用。最后，G蛋白偶联受体和G蛋白基因变异的表达在高血压血管舒张缺陷中的重要性仍存在争议。
血管系统中的G蛋白信号通路在高血压状态的发生和维持中均起重要作用。然而，G蛋白相关血管舒张途径中的任何单一缺陷都不太可能被证明是高血压的唯一原因。
