CARDIOPROTECTIVE ACTIONS OF VERAPAMIL ON THE BETA-ADRENERGIC-RECEPTORCOMPLEX IN ACUTE CANINE CHAGAS-DISEASE

The effect of verapamil treatment on the myocardial beta-adrenergic ad enylyl cyclase complex in acute canine Chagas' disease was investigate d. Relative to uninfected animals, 30 days of infection with T. cruzi reduced myocardial adenylyl cyclase activity by over 75%. With continu ous verapamil treatment, the infection-associated reduction in adenyly l cyclase activity was less than 50%. The individual components of the beta-adrenergic receptor complex were characterized. Infection: (1) i ncreased right ventricular (RV) beta-adrenergic receptor (beta AR) den sity five-fold: (2) decreased left ventricle beta AR density by 20%; ( 3) reduced the proportion of high-affinity beta AR receptors to the sa me extent in both left and right ventricles; (4) reduced alpha(s) by 5 0% as determined by Western blot analysis, increased alpha(i1-3) but d id not change alpha(o); and (5) decreased the magnitude of pertussis-t oxin-dependent [P-32]ADP ribosylation by 60% as well as the proportion of [P-32]ADP-ribose incorporated in alpha(o). Verapamil treatment of infected animals restored RV beta AR receptor density, alpha(s) and al pha(i1-3) to control levels but had no influence on any aspect of pert ussis-toxin-dependent [P-32]ADP-ribosylation. Verapamil treatment of u ninfected animals also: (1) increased beta-adrenergic adenylyl cyclase activity; (2) increased beta AR density in the RV but not the LV; (3) reduced high- to low-affinity beta-adrenergic receptors; and (4) affe cted only alpha(i2) (50% decrease). The results indicate that the majo r actions of verapamil on the beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardiopro tective effects. (C) 1996 Academic Press Limited