Cardioprotective Actions of Verapamil on theβ-Adrenergic Receptor Complex in Acute Canine Chagasʹ Disease

The effect of verapamil treatment on the myocardialβ-adrenergic adenylyl cyclase complex in acute canine Chagasʹ disease was investigated. Relative to uninfected animals, 30 days of infection withT. cruzireduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of theβ-adrenergic receptor complex were characterized. Infection: (1) increased right ventricular (RV)β-adrenergic receptor (βAR) density five-fold; (2) decreased left ventricleβAR density by 20%; (3) reduced the proportion of high-affinityβAR receptors to the same extent in both left and right ventricles; (4) reducedαsby 50% as determined by Western blot analysis, increasedαi1–3but did not changeαo; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated inαo. Verapamil treatment of infected animals restored RVβAR receptor density,αsandαi1–3to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increasedβ-adrenergic adenylyl cyclase activity; (2) increasedβAR density in the RV but not the LV; (3) reduced high- to low-affinityβ-adrenergic receptors; and (4) affected onlyαi2(50% decrease). The results indicate that the major actions of verapamil on theβ-adrenergic adenylyl cyclase complex in acute canine Chagas» disease may help to account for its cardioprotective effects.