Subsensitivity of cardiac beta-adrenoceptors in renal hypertensive rats

beta-Adrenoceptors were labeled with the selective beta-antagonist (-)[3H]dihydroalprenolol ([3H]DHA). Cardiac membranes isolated from renal hypertensive rats had the same density of adrenoceptors as normotensive rats (28 fmoles/mg of protein in both groups) but showed a significant elevation of the dissociation constant for [3H]DHA (Kd = 1.86 nM versus 1.04 nM for controls), indicating a reduced affinity of cardiac adrenoceptors for the radioligant. The lowered sensitivity to catecholamine is probably due to chronic exposure of beta-receptors to a high concentration of noradrenaline, whose turnover in cardiac nerves of renal hypertensive rats was significantly accelerated (turnover time 10.5 hr for hypertensive versus 17.2 for normotensive).