G-Protein-Coupled Receptor Kinase Activity in Hypertension : Increased Vascular and Lymphocyte G-Protein Receptor Kinase-2 Protein Expression

R. Gros, J. Chorazyczewski, M. D. Meek, J. L. Benovic, S. S. G. Ferguson, R. D. Feldman
2000 Hypertension  
Impaired receptor-stimulated adenylyl cyclase activation has been observed in lymphocytes from hypertensive subjects and has been linked to an increase in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression. However, whether the increase in lymphocyte GRK-2 reflected an increase in vascular GRK-2 was unknown. Therefore, we compared GRK-2 protein expression in lymphocytes and aortas obtained from normotensive Wistar rats, Wistar-Kyoto rats (WKY), and spontaneously hypertensive rats
more » ... (SHR) and from aortas of Dahl rats. Impaired ␤-adrenergic responsiveness was observed in lymphocytes and vascular tissues obtained from hypertensive SHR (10 and 15 weeks old) but not in those obtained from prehypertensive SHR (5 weeks old). Immunodetectable lymphocyte GRK-2 protein expression was increased in 10-week-old SHR (143Ϯ10% of the expression in 10-week-old Wistar rats and 131Ϯ11% of the expression in 10-week-old WKY, nϭ5 in each group). Immunodetectable vascular smooth muscle cell GRK-2 was comparably increased (169Ϯ14% of the expression in Wistar rats and 138Ϯ7% of the expression in WKY, nϭ5 in each group). Also, in hypertensive Dahl salt-sensitive rats, vascular GRK-2 protein expression was increased (185Ϯ14% of the expression in Dahl salt-resistant rats, nϭ5 in each group) compared with Dahl salt-resistant controls. These studies support a generalized defect in vascular GRK-2 protein expression in hypertension, which could be an important factor in the impairment of ␤-adrenergic-mediated vasodilation, characteristic of the hypertensive state. (Hypertension. 2000;35:38-42.)
doi:10.1161/01.hyp.35.1.38 pmid:10642272 fatcat:idxzgjkrg5gtpoz6bngoyt3zky