Cardioprotective actions of verapamil on the β-adrenergic receptor complex in acute canine Chagas' disease

Gexin Chen, Stephen Barr, Diane Walsh, Shira Rohde, Andrew Brewer, John P. Bilezikian, Murray Wittner, Herbert B. Tanowitz, Stephen A. Morris

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The effect of verapamil treatment on the myocardial β-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection with T. cruzi reduced 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 the β-adrenergic receptor complex were characterized. Infection: (1) increased right ventricular (RV) β-adrenergic receptor (βAR) density five-fold; (2) decreased left ventricle βAR density by 20%; (3) reduced the proportion of high-affinity βAR receptors to the same extent in both left and right ventricles; (4) reduced α(s) by 50% as determined by Western blot analysis, increased α(il-3) but did not change a0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in a0. Verapamil treatment of infected animals restored RV βAR receptor density, α(s) and α(il-3) to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increased β-adrenergic adenylyl cyclase activity; (2) increased βAR density in the RV but not the LV; (3) reduced high- to low-affinity β-adrenergic receptors; and (4) affected only α(i2) (50% decrease). The results indicate that the major actions of verapamil on the β-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardioprotective effects.

Original languageEnglish (US)
Pages (from-to)931-941
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number5
DOIs
Publication statusPublished - May 1996

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Keywords

  • Chagas' cardiomyopathy
  • Verapamil
  • b-adrenergic receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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