Effect of verapamil on the development of chronic experimental Chagas' disease

H. B. Tanowitz, S. A. Morris, Louis M. Weiss, J. P. Bilezikian, S. M. Factor, M. Wittner

Research output: Contribution to journalArticle

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Abstract

In previous work, we have shown that the chronic administration of verapamil, a calcium channel blocker, ameliorated the mortality, pathology, and biochemical alterations associated with acute murine Chagas' disease. To extend these studies to an esablished chronic model, C3H/Hej mice were infected with the Sylvio X10/4 clone. This clone does not cause symptomatic acute disease but does induce cardiac pathology incorporating several pathological features of human chagasic cardiomyopathy. Cardiac pathology was assessed at 60, 90, and 180 days postinfection. There was a significant decrease in the degree of inflammation and fibrosis in the group infected and treated with verapamil. Myocardial β-adrenergic adenylate cyclase (AC) activity was determined 180 days postinfection. In the infected group not treated with verapamil, there was no significant change in the maximum rate of conversion of ATP to cAMP (Vmax) or in the concentration of agonist giving 50% of Vmax (apparent Kact) for isoproterenol (ISPN)-dependent AC activation. The increase in Vmax for ISPN determined in the presence of 5'-guanylylimidodiphosphate (Gpp[NH]p) was consistently lower in infected than in uninfected mice, suggesting that infection altered the potential synergistic activation of AC by the guanine nucleotide. In the infected group treated with verapamil, there was a slight increase in the Vmax for ISPN. However, there was a marked enhancement of the synergistic contribution of Gpp(NH)p. These observations suggest that verapamil had preserved that aspect of the AC complex mediating guanine nucleotide sensitive activation of AC. Collectively, the observations in the acute and chronic models of murine Chagas' disease suggest that verapamil may be a useful adjunct in treatment.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume41
Issue number6
StatePublished - 1989

Fingerprint

Chagas Disease
Verapamil
Adenylyl Cyclases
Isoproterenol
Guanylyl Imidodiphosphate
Guanine Nucleotides
Pathology
Clone Cells
Inbred C3H Mouse
Calcium Channel Blockers
Acute Disease
Cardiomyopathies
Adrenergic Agents
Fibrosis
Adenosine Triphosphate
Inflammation
Mortality
Infection

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Tanowitz, H. B., Morris, S. A., Weiss, L. M., Bilezikian, J. P., Factor, S. M., & Wittner, M. (1989). Effect of verapamil on the development of chronic experimental Chagas' disease. American Journal of Tropical Medicine and Hygiene, 41(6), 643-649.

Effect of verapamil on the development of chronic experimental Chagas' disease. / Tanowitz, H. B.; Morris, S. A.; Weiss, Louis M.; Bilezikian, J. P.; Factor, S. M.; Wittner, M.

In: American Journal of Tropical Medicine and Hygiene, Vol. 41, No. 6, 1989, p. 643-649.

Research output: Contribution to journalArticle

Tanowitz, HB, Morris, SA, Weiss, LM, Bilezikian, JP, Factor, SM & Wittner, M 1989, 'Effect of verapamil on the development of chronic experimental Chagas' disease', American Journal of Tropical Medicine and Hygiene, vol. 41, no. 6, pp. 643-649.
Tanowitz, H. B. ; Morris, S. A. ; Weiss, Louis M. ; Bilezikian, J. P. ; Factor, S. M. ; Wittner, M. / Effect of verapamil on the development of chronic experimental Chagas' disease. In: American Journal of Tropical Medicine and Hygiene. 1989 ; Vol. 41, No. 6. pp. 643-649.
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