Effects of lindane (gamma-hexachlorocyclohexane) on rat heart muscle contraction.
The effects of micromolar concentrations of lindane on the mechanical activity of cardiac left ventricular papillary muscles were studied in adult female rats. Lindane decreased the amplitude and duration of the contraction, and slowed down the time course of its ascending phase (i.e. decreased the maximum rate of rise of the initial phase (dC/dt(max))). Both amplitude and duration of the contraction, but not dC/dt(max), were restored by subsequent application of the rapid delayed outward K(+) current (I(Kr)) blocker E-4031 (10 nmol/l). Increasing the stimulation frequency from 1 to 3.3 Hz in the control solution produced a decrease in the amplitude of the first beat peak contraction while a slow recovery phase (srp) developed, as the result of the Na(+)-Ca(2+) exchanger activity. When the frequency was restored to 1 Hz, a post rest potentiation (prp) with a negative staircase (ns) developed due to the sarcoplasmic reticulum (SR) Ca(2+) refilling. Lindane increased the amplitude of both srp and prp, but did not affect ns, which indicates that SR Ca(2+) refilling was not altered by the pesticide. In conclusion, the results strongly suggest that some of the lindane-induced negative inotropic and chronotropic-like effects on the contraction are due to an increased I(Kr) while the decrease in dC/dt(max) (i.e. the rate of cross-bridge formation) results from lindane oxidative properties.
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Laboratoire d'Optique et Biosciences, INSERM U 696 - CNRS UMR 7645 - X/ENSTA, Ecole Polytechnique, 91128 Palaiseau Cedex, France.
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D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function
D001556:Hexachlorocyclohexane