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 regulating the interaction between G-protein-coupled receptors and activation of adenylyl cyclase. However, it was not known whether this increase in GRK-2 protein expression was attributable to regulation at the level of translation. Furthermore, the relationship between extent of GRK-2 expression, receptor activation of adenylyl cyclase, and blood pressure was unclear. We therefore studied lymphocytes from 7 young subjects with borderline hypertension and 14 young normotensive subjects. Immunodetectable GRK-2 protein expression in lymphocytes from subjects with hypertension was increased (155%+/-7% of normotensive subjects; P < .05). In addition, GRK-2 protein expression was positively correlated with blood pressure (r = 0.53; P = .013) and inversely correlated with beta-adrenergic-mediated adenylyl cyclase activity (r = -0.54, P = .012). However, lymphocyte GRK-2 messenger ribonucleic acid (mRNA) content was not altered (110%+/-13% of that observed in normotensive control subjects). Increased GRK-2 protein expression may be an important factor in the impairment of beta-adrenergic-mediated vasodilation, characteristic of the hypertensive state.
Gros
R
R
Department of Medicine, University of Western Ontario, and the John P. Robarts Research Institute, London, Canada.
Tan
C M
CM
Chorazyczewski
J
J
Kelvin
D J
DJ
Benovic
J L
JL
Feldman
R D
RD
D000328:Adult; D001794:Blood Pressure; D015152:Blotting, Northern; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051552:beta-Adrenergic Receptor Kinases
D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases