Effects of verapamil on acute murine Chagas' disease

Herbert B. Tanowitz, Murray Wittner, Bing Chen, Huan Huang, Louis M. Weiss, George J. Christ, Vicki Braunstein, John P. Bilezikian, Stephen A. Morris

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14 Scopus citations

Abstract

Continuous administration of verapamil significantly reduced the mortality rate of acute murine Trypanosoma cruzi infection (P < 0.05). The mechanistic basis for these observations was investigated. Verapamil and other calcium-channel blockers did not inhibit the growth of epimastigotes in culture. Furthermore, verapamil did not inhibit the intracellular growth of amastigotes in endothelial cells as determined by the uptake of 3H-uracil. There were no significant differences in parasitemia between infected mice that were untreated and those treated with verapamil. Twenty days postinfection infected, untreated mice had a parasitemia of 5.8 x 106 trypomastigotes/ml (SD ± 2 x 106), whereas infected, verapamil-treated mice had a parasitemia of 2.2 x 106 trypomastigotes/ml (SD ± 0.5 x 106). There was no significant difference in mortality between mice administered verapamil only for the initial 10 days of murine infection compared to those treated continuously. A 3-day delay in the initiation of verapamil administration reduced the mortality rate, but a 10-day delay did not. Propranolol (β-adrenergic blocker), prazosin (α1-adrenergic blocker), and diltiazem (another calcium-channel blocker) reduced the mortality but not significantly (P = 0.07). In biochemical studies of the β- adrenergic signal transduction complex, we determined that verapamil and propranolol reversed the infection-associated decrease in myocardial β- adrenergic adenylyl cyclase activity. In contrast, complementary western blot analysis revealed no significant changes in the G-proteins of the β- adrenergic receptor complex 45 days postinfection. Therefore, these results suggest that the basis of verapamil's influence on the early critical period of infection is multifactorial and independent of a direct trypanocidal effect.

Original languageEnglish (US)
Pages (from-to)814-819
Number of pages6
JournalJournal of Parasitology
Volume82
Issue number5
DOIs
StatePublished - Oct 1996

ASJC Scopus subject areas

  • Parasitology
  • Ecology, Evolution, Behavior and Systematics

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    Tanowitz, H. B., Wittner, M., Chen, B., Huang, H., Weiss, L. M., Christ, G. J., Braunstein, V., Bilezikian, J. P., & Morris, S. A. (1996). Effects of verapamil on acute murine Chagas' disease. Journal of Parasitology, 82(5), 814-819. https://doi.org/10.2307/3283896