G-protein-coupled receptor kinase activity in hypertension - Increased vascular and lymphocyte G-protein receptor kinase-2 protein expression

Impaired receptor-stimulated adenylyl cyclase activation has been observed in lymphocytes from hypertensive subjects and has been linked to an increas e in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression. How ever, whether the increase in lymphocyte GRK-2 reflected an increase in vas cular GRK-2 was unknown. Therefore, we compared GRK-2 protein expression in lymphocytes and aortas obtained from normotensive Wistar rats, Wistar-Kyot o rats (WKY), and spontaneously hypertensive rats (SHR) and from aortas of Dahl rats. Impaired beta-adrenergic responsiveness was observed in lymphocy tes and vascular tissues obtained from hypertensive SHR (10 and 15 weeks ol d) but not in those obtained from prehypertensive SHR (5 weeks old). Immuno detectable lymphocyte GRK-2 protein expression was increased in 10-week-old SHR (143+/-10% of the expression in 10-week-old Wistar rats and 131+/-11% of the expression in 10-week-old WKY, n=5 in each group). Immunodetectable vascular smooth muscle cell GRK-2 was comparably increased (169+/-14% of th e expression in Wistar rats and 138+/-7% of the expression in WKY, n=5 in e ach group). Also, in hypertensive Dahl salt-sensitive rats, vascular GRK-2 protein expression was increased (185+/-14% of the expression in Dahl salt- resistant rats, n=5 in each group) compared with Dahl salt-resistant contro ls. These studies support a generalized defect in vascular GRK-2 protein ex pression in hypertension, which could be an important factor in the impairm ent of beta-adrenergic-mediated vasodilation, characteristic of the hyperte nsive state.