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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Chagas disease
verapamil
Chagas Disease
Verapamil
mortality
mice
Parasitemia
calcium
parasitemia
trypomastigotes
calcium channel blockers
propranolol
Adrenergic Antagonists
Mortality
Calcium Channel Blockers
Infection
Propranolol
infection
Adrenergic Agents
epimastigotes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Parasitology
  • Microbiology

Cite this

Effects of verapamil on acute murine Chagas' disease. / Tanowitz, Herbert B.; Wittner, Murray; Chen, Bing; Huang, Huan; Weiss, Louis M.; Christ, George J.; Braunstein, Vicki; Bilezikian, John P.; Morris, Stephen A.

In: Journal of Parasitology, Vol. 82, No. 5, 10.1996, p. 814-819.

Research output: Contribution to journalArticle

Tanowitz, HB, Wittner, M, Chen, B, Huang, H, Weiss, LM, Christ, GJ, Braunstein, V, Bilezikian, JP & Morris, SA 1996, 'Effects of verapamil on acute murine Chagas' disease', Journal of Parasitology, vol. 82, no. 5, pp. 814-819. https://doi.org/10.2307/3283896
Tanowitz, Herbert B. ; Wittner, Murray ; Chen, Bing ; Huang, Huan ; Weiss, Louis M. ; Christ, George J. ; Braunstein, Vicki ; Bilezikian, John P. ; Morris, Stephen A. / Effects of verapamil on acute murine Chagas' disease. In: Journal of Parasitology. 1996 ; Vol. 82, No. 5. pp. 814-819.
@article{a0d0a2fc15304b41a89f9a19617d496a,
title = "Effects of verapamil on acute murine Chagas' disease",
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.",
author = "Tanowitz, {Herbert B.} and Murray Wittner and Bing Chen and Huan Huang and Weiss, {Louis M.} and Christ, {George J.} and Vicki Braunstein and Bilezikian, {John P.} and Morris, {Stephen A.}",
year = "1996",
month = "10",
doi = "10.2307/3283896",
language = "English (US)",
volume = "82",
pages = "814--819",
journal = "Journal of Parasitology",
issn = "0022-3395",
publisher = "American Society of Parasitologists",
number = "5",

}

TY - JOUR

T1 - Effects of verapamil on acute murine Chagas' disease

AU - Tanowitz, Herbert B.

AU - Wittner, Murray

AU - Chen, Bing

AU - Huang, Huan

AU - Weiss, Louis M.

AU - Christ, George J.

AU - Braunstein, Vicki

AU - Bilezikian, John P.

AU - Morris, Stephen A.

PY - 1996/10

Y1 - 1996/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029821843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029821843&partnerID=8YFLogxK

U2 - 10.2307/3283896

DO - 10.2307/3283896

M3 - Article

VL - 82

SP - 814

EP - 819

JO - Journal of Parasitology

JF - Journal of Parasitology

SN - 0022-3395

IS - 5

ER -