Beta-adrenergic receptor differences in cultured arterial smooth muscle cells between spontaneously hypertensive and Wistar-Kyoto rats.
In this study, beta-adrenergic receptors of cultured arterial smooth muscle cells (ASMC) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared. Scatchard analysis of [3H]-dihydroalprenolol hydrochloride (DHA) binding revealed that the maximum binding capacity (Bmax) for [3H]-DHA binding was significantly higher in WKY than in SHR, by twofold (n = 6, P less than 0.0001). Analysis of isoproterenol competition for [3H]-DHA binding by computerized non-linear regression indicated that the two strains have an equal number of high-affinity-state receptors, but that WKY rats have about three times more low-affinity-state receptors than SHR. Isoproterenol stimulated cyclic adenosine monophosphate (cAMP) production in a dose-dependent manner, and dose-response experiments revealed an effective concentration of ligand at which 50% of the maximum effect is observed (EC50) of 5-10 x 10(-8) mol/l isoproterenol for both WKY and SHR. Also, isoproterenol-stimulated cAMP production was inhibited by propranolol in a dose-dependent manner. This study demonstrates that the previously described difference observed for in vivo binding of beta-adrenergic receptors of vessels from SHR is retained in tissue culture of vascular smooth muscle and is, therefore, independent of the elevated plasma catecholamine and blood pressure levels found in SHR. The finding that there is equal cAMP stimulation in WKY and SHR is consistent with the discovery of an equal number of high-affinity-state receptors in the two strains. The difference in total beta-adrenergic receptor number is secondary to the greater number of low-affinity-state receptors found in WKY.
Jazayeri
A
A
Department of Human Biological Chemistry, University of Texas Medical Branch, Galveston 77550.
Meyer
W J
WJ
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006973:Hypertension / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol