Calcium channel blockade with verapamil effects on blood pressure, renal, and myocardial adrenergic, cholinergic, and calcium channel receptors in inbred dahl hypertension-sensitive (S/jr) and hypertension-resistant (r/jr) rats

Abstract

Verapamil HCl was chronically administered to inbred Dahl S/JR and R/JR rats maintained on a diet containing 8.0% NaCl (w/w) and the effects on blood pressure (BP) and heart rate (HR) were investigated. Treatment over a 4-week period via implanted miniosmotic pumps attenuated but did not prevent the development of salt-induced hypertension (HT) in the S/JR rat. Elevated HR, possibly reflexive in origin, was observed in S/JR rats that received verapamil but not in similarly treated R/JR rats. Although verapamil retarded the development of HT in S/JR rats, BP rose to moderately hypertensive levels, and the ventricle/body weight ratio was elevated by the termination of the study. The effect of verapamil on the density and affinity of α1-, α2-, and beta-adrenergic; muscarinic cholinergic, and calcium channel receptors in renal and ventricular membranes was also assessed. The density of renal and ventricular α- and beta-adrenoceptors was not affected by chronic drug treatment. The density of renal α- and beta-adrenoceptors was greater in the S/JR strain than in the R/JR strain, regardless of the treatment. The density of muscarinic cholinergic and calcium channel receptors in the ventricle was not affected by the treatment. The results of this study suggest that the long-term antihypertensive effects of verapamil in the S/JR rat do not involve an alteration in the binding characteristics of adrenergic, cholinergic, or calcium channel receptor sites in ventricular and renal membranes. Although the density of renal αα2-and beta-adrenoceptors was greater in the S/JR strain than in the R/JR strain, these differences are related to the genetic predisposition to HT and not the treatment with verapamil. Am J Hypertens 1988;1:255S-262S. © 1988 by the American Journal of Hypertension, Ltd.