Impaired desensitization of cardiac beta-adrenoceptors in the spontaneously hypertensive rat.
Reduced inotropic responsiveness by spontaneously hypertensive rats (SHR) to beta agonists is associated with, and may be secondary to, a decline in cardiac membrane-bound beta adrenoceptors. It is widely assumed that this decline reflects a desensitization of the receptor secondary to enhanced sympathetic drive, but direct evidence is lacking. We examined this issue in cell-free cardiac preparations from age-matched SHR and Wistar-Kyoto (WKY) rats. Isoproterenol induced a time- and concentration-dependent decline in membrane-bound beta receptors but was considerably more effective in WKY than in SHR (43% decline versus 29% in SHR, P less than 0.01). Since cyclic AMP-protein kinase inhibitor prevented only 15-20% of the isoproterenol-induced decline, this was probably mediated by the beta receptor kinase. Cyclic AMP-dependent protein kinase induced a 38% desensitization in WKY rats but was completely ineffective in SHR. These results suggest that desensitization of the beta receptor is impaired in SHR, probably because the structural organization of the receptor in the cardiac membranes is altered.
Limas
C
C
Department of Laboratory Medicine, University of Minnesota School of Medicine, Minneapolis.
Limas
C J
CJ
D000818:Animals; D002474:Cell-Free System; D006321:Heart / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000502:physiology* / Q000648:ultrastructure
D011943:Receptors, Adrenergic, beta; D011494:Protein Kinases; D007545:Isoproterenol