G-PROTEIN-COUPLED RECEPTOR KINASE-ACTIVITY IS INCREASED IN HYPERTENSION

Impaired vascular beta-adrenergic responsiveness may play an important role in the development and/or maintenance of hypertension. This defe ct has been associated with an alteration in receptor/guanine nucleoti de regulatory protein (G-protein) interactions. However, the locus of this defect remains unclear. G-Protein-coupied receptor kinases (GRKs) phosphorylate serine/threonine residues on G-protein-linked receptors in an agonist-dependent manner. GRK activation mediates reduced recep tor responsiveness and impaired receptor/G-protein coupling. To determ ine whether the impairment in beta-adrenergic response in human hypert ension might be associated with altered GRK activity, we studied lymph ocytes from younger hypertensive subjects as compared with older and y ounger normotensive subjects. We assessed GRK activity by rhodopsin ph osphorylation and GRK expression by immunoblot. GRK activity was signi ficantly increased in lymphocytes from younger hypertensive subjects a nd paralleled an increase in GRK-2 (beta ARK-1) protein expression. In contrast, no alterations in cAMP-dependent kinase (A-kinase) activity or GRK-5/6 expression were noted. GRK activity was not increased in l ymphocytes from older normotensive subjects who demonstrated a similar impairment in beta-adrenergic-mediated adenylyl cyclase activation. T hese studies indicate that GRK activity is selectively increased in ly mphocytes from hypertensive subjects. The increase in GRK activity may underlie the reduction in beta-adrenergic responsiveness characterist ic of the hypertensive state.