β-Adrenoceptors and Responsiveness in Cardiac Hypertrophy Associated with Renal Hypertension in Renovascular Hypertensive Rats

Abstract

1. The possible contribution of changes in cardiac β-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 β-adrenoceptors ([3H)dihydroalprenolol, [3H]DHA) were then assayed in the same 44 hearts. 2. There was no difference between renovascular hypertensive rats (RHR) and matched normotensive controls as regards chronotropic responses to isoprenaline or in atrial β-adrenoceptor numbers or apparent affinity. 3. Inotropic responses were significantly lower in all stages of RHR than in matched normotensive controls. 4. There was also a significant (P < 0.001) decrease in ventricular β-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 β-adrenoceptor density (r = 0.54, P = 0.0005). 5. These results suggest that the reduction of ventricular β-adrenoceptor density in that model of hypertension was responsible, at least partially, for the lowered inotropic responsiveness of the same hearts to isoprenaline.