An increase in cardiac alpha₁-adrenoceptors following chronic clonidine treatment

Chronic treatment (22 days) of rats with clonidine (0.5 mg/kg s.c. twice a day followed by 20 h of withdrawal) resulted in a significant increase in the specific [³H]WB4101 binding to ventricular and intraventricular septal α₁-adrenoceptors but no alteration of the atrial α₁-adrenoceptors. Scatchard analysis indicated that the increase in the [³H]WB4101 binding to the clonidine-treated cardiac tissues was due to an enhancement of the α₁-adrenoceptor density since there was a significant increase in the B_max value for the [³H]WB4101 binding to the treated ventricles without a change in the K_d value. The specific [³H]WB4101 binding to cardiac α₁-adrenoceptors was not altered by the acute (1 day) or 7 days treatment with clonidine. Chronic treatment with clonidine had no significant effect on the specific [³H](-)DHA binding to the atrial and ventricular β-adrenoceptors. The noradrenaline (NA) concentrations in the clonidine-treated ventricles and intraventricular septae were decreased by 16-20%. These data provide biochemical evidence compatible with a significant reduction of sympathetic outflow to the ventricular myocardium by clonidine.