Biphasic effect of SIN-1 is reliant upon cardiomyocyte contractile state.

Free Radical Biology & Medicine
Mark J KohrM T Ziolo

Abstract

Many studies have demonstrated a biphasic effect of peroxynitrite in the myocardium, but few studies have investigated this biphasic effect on beta-adrenergic responsiveness and its dependence on contractile state. We have previously shown that high 3-morpholinosydnonimine (SIN-1) (source of peroxynitrite, 200 micromol/L) produced significant anti-adrenergic effects during maximal beta-adrenergic stimulation in cardiomyocytes. In the current study, we hypothesize that the negative effects of high SIN-1 will be greatest during high contractile states, whereas the positive effects of low SIN-1 (10 micromol/L) will predominate during low contractility. Isolated murine cardiomyocytes were field stimulated at 1 Hz, and [Ca(2+)](i) transients and shortening were recorded. After submaximal isoproterenol (ISO) (beta-adrenergic agonist, 0.01 micromol/L) stimulation, 200 micromol/L SIN-1 induced two distinct phenomena. Cardiomyocytes undergoing a large response to ISO showed a significant reduction in contractility, whereas cardiomyocytes exhibiting a modest response to ISO showed a further increase in contractility. Additionally, 10 micromol/L SIN-1 always increased contractility during low ISO stimulation, but had no effect during maxi...Continue Reading

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Citations

Apr 11, 2008·American Journal of Physiology. Cell Physiology·Honglan WangMark T Ziolo
Jan 2, 2014·Pharmacology & Therapeutics·Lifei TangMark T Ziolo
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Aug 30, 2008·Journal of Molecular and Cellular Cardiology·Mark T ZioloHonglan Wang
Sep 29, 2011·Journal of Molecular and Cellular Cardiology·Yin Hua Zhang, Barbara Casadei
Jan 18, 2015·Journal of Molecular and Cellular Cardiology·Steve R RoofMark T Ziolo

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