Beta-adrenoceptors and responsiveness in cardiac hypertrophy associated with renal hypertension in renovascular hypertensive rats.

The possible contribution of changes in cardiac beta-adrenoceptors to alterations in cardiac responses to isoprenaline were investigated in hearts isolated from rats with renovascular hypertension (two-kidney, one-clip Goldblatt), 6, 12 and 18 weeks after renal artery clipping. Cardiac responses were determined in vitro (Langendorff preparation), and ventricular beta-adrenoceptors [( 3H]dihydroalprenolol, [3H]DHA) were then assayed in the same 44 hearts. There was no difference between renovascular hypertensive rats (RHR) and matched normotensive controls as regards chronotropic responses to isoprenaline or in atrial beta-adrenoceptor numbers or apparent affinity. Inotropic responses were significantly lower in all stages of RHR than in matched normotensive controls. There was also a significant (P less than 0.001) decrease in ventricular beta-adrenoceptor density with no significant change in apparent affinity (Kd). Inotropic responsiveness to isoprenaline (max. increment in peak dP/dt) was significantly correlated with ventricular beta-adrenoceptor density (r = 0.54, P = 0.0005). These results suggest that the reduction of ventricular beta-adrenoceptor density in that model of hypertension was responsible, at least partially, for the lowered inotropic responsiveness of the same hearts to isoprenaline.