Defective vasodilatory mechanisms in hypertension: a G-protein-coupled receptor perspective

Abstract

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.