Pharmacology & Toxicology Poster Session
Chorazyczewski, J (Depts of Medicine, Pharmacology & Toxicology, University of Western Ontario, Canada)
Tan, CM (Depts of Medicine , Pharmacology & Toxicology, University of Western Ontario, Canada)
Benovic, JL (Dept of Biochemistry and molecular pharmacology, Tomas Jefferson University, PA, USA)
Kelvin, DJ (John P. Robarts Research Institute, Canada)
Feldman, RD (Depts of Medicine, Pharmacology & Toxicology, and Physiology, University of Western Ontario, Canada)
In human hypertension there is an impairment of beta-adrenergic responsiveness, which parallels an increase in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression. However, whether changes in lymphocyte GRK-2 parallel alterations in vascular GRK-2 and whether this increase is due to regulation at the level of translation was unknown. To determine if increased GRK-2 protein expression in hypertensive subjects paralleled increased GRK-2 mRNA we studied lymphocytes from young borderline hypertensive (H, n=7) and young normotensive subjects (N, n=14). Immunodetectable lymphocyte GRK-2 protein expression in H was increased (155+/-7% of N, p < 0.05) and was inversely correlated with beta-adrenergic-mediated adenylyl cyclase activity and positively correlated with blood pressure. However, lymphocyte GRK-2 mRNA content was not altered in H (110+/-13% of N). To determine if lymphocyte GRK-2 protein expression paralleled alterations in vascular GRK-2 we studied lymphocytes and aortae obtained from normotensive Wistar (W) and WKY rat controls versus spontaneously hypertensive rats (SHR), which also demonstrate impaired beta-adrenergic responsiveness. Immunodetectable lymphocyte GRK-2 protein expression was increased in SHR (143+/-10% of the expression in W and 131+/-11% of WKY). Immunodetectable vascular myocyte GRK-2 was comparably increased in SHR (169+/-14% of expression in W and 183+/-8% of the expression in WKY). These studies indicate that GRK-2 protein expression is increased in both hypertensive subjects and SHR. This increase in lymphocyte GRK-2 parallels increased vascular GRK-2 protein expression, but was not associated with altered lymphocyte GRK-2 mRNA content.
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|Gros, R; Chorazyczewski, J; Tan, CM; Benovic, JL; Kelvin, DJ; Feldman, RD; (1998). G-Protein Coupled Receptor Kinase-2 Regulation In Hypertension. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/pharmtox/gros0775/index.html|
|© 1998 Author(s) Hold Copyright|