Adrenoceptor recovery after heart failure in the dog

Abstract

The role of myocardial beta receptors in pacing induced congestive heart failure is uncertain. The aims of the study were therefore (1) to examine total beta adrenoceptor density in canine left ventricle during pacing induced heart failure; and (2) to evaluate whether there is a relationship between beta adrenoceptor numbers and circulating noradrenaline during progression of heart failure. Heart failure was examined at different stages: early (after 1 week of pacing at 250 beats.min-1); peak (after 4 weeks of pacing); and after recovery (4 weeks after pacing was discontinued). Myocardial beta adrenoceptor density was assessed by radioligand binding with iodocyanopindolol. Plasma noradrenaline was determined by high performance liquid chromatography with electrochemical detection. Compared to control, left ventricular beta adrenoceptor density was: (1) not significantly different in early heart failure, at 2540(SEM 460) v 3160(260) fmol.g-1 wet weight in control; (2) decreased 63% at peak heart failure [1180(100) fmol.g-1, p < 0.01]; and (3) restored to control density after recovery from heart failure [3430(540) fmol.g-1]. The beta adrenoceptor dissociation constant was unaltered throughout. There was an inverse correlation between myocardial beta adrenoceptor density and plasma noradrenaline (r = -0.785, p < 0.01). The progressive decline in beta adrenoceptor density as heart failure develops and the capacity of beta adrenoceptors to return to control levels after recovery from the experimental heart failure state suggests that there is a reversible abnormality in beta adrenoceptors during heart failure.