(Hypertension. 2000;35:38.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
G-Protein–Coupled Receptor Kinase Activity in Hypertension
Increased Vascular and Lymphocyte G-Protein Receptor Kinase-2 Protein Expression
From the Departments of Medicine, Physiology and Pharmacology and Toxicology (R.G., J.C., M.D.M., R.D.F.), University of Western Ontario, London, Ontario, Canada; the John P. Robarts Research Institute (S.S.G.F., R.D.F.), London, Ontario, Canada; and the Department of Biochemistry and Molecular Pharmacology (J.L.B.), Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Dr Ross D. Feldman, Room 6L13B, LHSC-University Campus, 339 Windermere Rd, PO Box 5339, London, Ontario. Canada N6A 5A5. E-mail feldmanr{at}lhsc.on.ca
Abstract—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 (SHR) and from aortas of Dahl rats. Impaired ß-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 (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 the expression in Wistar rats and 138±7% of the expression in WKY, n=5 in each 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 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 ß-adrenergic–mediated vasodilation, characteristic of the hypertensive state.
Key Words: G protein • adrenergic receptors • adenylyl cyclase • hypertension, essential • cyclic AMP • rats
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