Differential changes of myocardial beta-adrenoceptor subtypes and G-proteins in dogs with right-sided congestive heart failure

We have shown previously in dogs with right heart failure that the reduction of myocardial beta-adrenoceptor density occurs only in the failing right ventricle, while cardiac inotropic responses to beta-adrenergic stimulation are reduced in both the right and left ventricles. The purpose of the present study was to determine whether a post-receptor defect in the guanine nucleotide-binding regulatory proteins (G-proteins) existed which would explain, at least in part, the adrenergic subsensitivity in both ventricles of the heart failure dogs. Using both immunoblotting technique and the bacterial toxin-mediated ADP ribosylation assays, we found that the stimulatory G-protein (G(s)) was reduced in both ventricles of the heart failure dogs. In contrast, there were no changes in the inhibitory G-protein (G(i)). In addition, receptor subtype analysis showed that only beta(1)-adrenoceptors were reduced in the failing right ventricle of the heart failure animals. This study demonstrated that the reduction of beta-adrenoceptors in right heart failure was chamber-specific whereas the reduction of G(s) was non-selective, occurring in both ventricles of right heart failure dogs. The findings further suggest that the reduction of G(s) probably was caused by systemic neurohormonal activation, independent of local ventricular stress.