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Title: Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased. beta. -adrenergic responsiveness and evidence of increased intracellular calcium

Abstract

The heart has not been regarded as a major target organ of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity notwithstanding that lethal cardiac dysfunction can occur in the absence of histopathological changes. To assess possible TCDD cardiotoxicity, the authors studied the effect of TCDD five days after treatment on the contractility of guinea pig right ventricular papillary muscle. TCDD treatment significantly decreased ..beta..-adrenergic responsiveness. In papillary muscles from TCDD-treated guinea pigs, the positive inotropic effect on isoproterenol was decreased by a mean of 65%, and the enhancement in the velocity of relaxation was 60% less than in the controls. On the other hand, TCDD treatment did not alter the positive inotropic effect of lower concentrations of isoproterenol. After TCDD, responsiveness to low-frequency stimulation was enhanced, responsiveness to increases in extracellular Ca/sup 2 +/ concentration was attenuated, and isoproterenol-elicited aftercontractions in K/sup +/-depolarized preparations were increased in magnitude. Collectively, the latter findings suggest that in addition to decreasing ..beta..-adrenergic responsiveness, TCDD increases the intracellular Ca/sup 2 +/ concentration in papillary muscle. The findings indicate that TCDD causes a specific pattern of cardiac dysfunction in a mammalian species, selectively augmenting or decreasing different cardiac responses. The cardiac changes are consistent with reported membrane effects of TCDD;more » further, they suggest that the heart may be a major target organ for TCDD toxicity.« less

Authors:
; ;
Publication Date:
Research Org.:
Cornell Univ. Medical College, New York, NY (USA)
OSTI Identifier:
6647648
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. U.S.A.; (United States)
Additional Journal Information:
Journal Volume: 85:3
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; CALCIUM COMPOUNDS; UPTAKE; DIOXIN; BIOLOGICAL EFFECTS; HEART; PHYSIOLOGY; DOSE-RESPONSE RELATIONSHIPS; GUINEA PIGS; MUSCLES; POTASSIUM COMPOUNDS; SYMPATHOMIMETICS; ALKALI METAL COMPOUNDS; ALKALINE EARTH METAL COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARDIOVASCULAR SYSTEM; DRUGS; HETEROCYCLIC COMPOUNDS; MAMMALS; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANS; RODENTS; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology

Citation Formats

Canga, L, Levi, R, and Rifkind, A B. Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased. beta. -adrenergic responsiveness and evidence of increased intracellular calcium. United States: N. p., 1988. Web. doi:10.1073/pnas.85.3.905.
Canga, L, Levi, R, & Rifkind, A B. Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased. beta. -adrenergic responsiveness and evidence of increased intracellular calcium. United States. https://doi.org/10.1073/pnas.85.3.905
Canga, L, Levi, R, and Rifkind, A B. 1988. "Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased. beta. -adrenergic responsiveness and evidence of increased intracellular calcium". United States. https://doi.org/10.1073/pnas.85.3.905.
@article{osti_6647648,
title = {Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased. beta. -adrenergic responsiveness and evidence of increased intracellular calcium},
author = {Canga, L and Levi, R and Rifkind, A B},
abstractNote = {The heart has not been regarded as a major target organ of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity notwithstanding that lethal cardiac dysfunction can occur in the absence of histopathological changes. To assess possible TCDD cardiotoxicity, the authors studied the effect of TCDD five days after treatment on the contractility of guinea pig right ventricular papillary muscle. TCDD treatment significantly decreased ..beta..-adrenergic responsiveness. In papillary muscles from TCDD-treated guinea pigs, the positive inotropic effect on isoproterenol was decreased by a mean of 65%, and the enhancement in the velocity of relaxation was 60% less than in the controls. On the other hand, TCDD treatment did not alter the positive inotropic effect of lower concentrations of isoproterenol. After TCDD, responsiveness to low-frequency stimulation was enhanced, responsiveness to increases in extracellular Ca/sup 2 +/ concentration was attenuated, and isoproterenol-elicited aftercontractions in K/sup +/-depolarized preparations were increased in magnitude. Collectively, the latter findings suggest that in addition to decreasing ..beta..-adrenergic responsiveness, TCDD increases the intracellular Ca/sup 2 +/ concentration in papillary muscle. The findings indicate that TCDD causes a specific pattern of cardiac dysfunction in a mammalian species, selectively augmenting or decreasing different cardiac responses. The cardiac changes are consistent with reported membrane effects of TCDD; further, they suggest that the heart may be a major target organ for TCDD toxicity.},
doi = {10.1073/pnas.85.3.905},
url = {https://www.osti.gov/biblio/6647648}, journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = ,
volume = 85:3,
place = {United States},
year = {1988},
month = {2}
}