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The thromboxane A2 mimic U46619 increases calcium transients in rat cardiac myocytes.
Heinroth-Hoffmann-I; Hoffmann-P; Toraason-M
Toxicologist 1992 Feb; 12(1):383
Cardiotoxicity of the endogenous arachidonic acid metabolite thromboxane A2 (TXA2) is presumed to arise indirectly from its induction of vasoconstriction and platelet aggregation. However, direct effects of TXA2 on the myocardium have not been described in the literature. Recent reports indicate that TXA2 induced platelet aggregation is associated with an increase in cytosolic Ca. The present study was designed to determine if TXA2 had a comparable effect on intracellular Ca transients (measured with fura-2) in isolated cardiac myocytes from neonatal rats. The TXA2 mimic U46619 (0.1 - 1 microM) markedly increased the height and width of electrically (I Hz, 60 V, 10 ms) induced Ca transients. This effect was accompanied by elevation of diastolic Ca concentration and arrhythmic events. The effects of U46619 were not reversible upon washout, but were antagonized by equimolar concentrations of the TXA2 receptor antagonist BM 13.177. The role of transsarcolemmal Ca fluxes, and sarcoplasmic reticulum Ca release and sequestration where investigated with potassium induced depolarization, verapamil, caffeine, ryanodine, and dibutyryl cAMP. Results are consistent with the hypothesis that the cardiotoxicity of TXA2 is associatied with its direct effect on myocardial Ca dynamics.
Laboratory-animals; Cardiovascular-function; Cardiovascular-function-tests; Cardiovascular-system-disease; Platelets; Cardiovascular-system-disorders; Heart
Issue of Publication
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division