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


RESULTS
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.


CONCLUSIONS
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.
Feldman
Ross D
RD
Cell Signaling and Vascular Biology Research Groups, Robarts Research Institute, London, Ontario, Canada.
Gros
Robert
R
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018450:Disease Progression; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; D017346:Protein Serine-Threonine Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6; C517898:GRK5 protein, human; C517897:Grk5 protein, rat; D000262:Adenylyl Cyclases