G-protein-coupled receptor kinase expression in hypertension

In human hypertension we have recently identified an increase in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression, the key protein re gulating the interaction between G-protein-coupled receptors and activation of adenylyl cyclase, However, it was not known whether this increase in GR K-2 protein expression was attributable to regulation at the level of trans lation, furthermore, the relationship between extent of GRK-2 expression, r eceptor activation of adenylyl cyclase, and blood pressure was unclear. We therefore studied lymphocytes from 7 young subjects with borderline hyperte nsion and 14 young normotensive subjects, Immunodetectable GRK-2 protein ex pression in lymphocytes from subjects with hypertension was increased (155% +/- 7% of normotensive subjects; P < .05), In addition, GRK-2 protein expr ession was positively correlated with blood pressure (r = 0.53; P = .013) a nd inversely correlated with beta-adrenergic-mediated adenylyl cyclase acti vity (r = -0.54, P = .012), However, lymphocyte GRK-2 messenger ribonucleic acid (mRNA) content was not altered (110% +/- 13% of that observed in norm otensive control subjects). Increased GRK-2 protein expression may be an im portant factor in the impairment of beta-adrenergic-mediated vasodilation, characteristic of the hypertensive state.