The direct inotropic effect of hypertonic mannitol was compared in isolated rat and cat papillary muscles. The inotropic effects of paired electrical stimulation and D600 were also evaluated in the same species. At extracellular calcium concentrations of 2.5 mM, hypertonic mannitol (25--100 mosmol/kg H2O above normal) depressed contractility in isolated rat myocardium; hyperosmolality exerted a positive effect only when extracellular Ca2+ was low (e.g., 0.3 mM). Paired pacing exerted a small but significant inotropic effect in rat heart when extracellular Ca2+ was 2.5 mM, and a larger effect at lower Ca2+. As previously noted, hypertonic mannitol and paired pacing both produced significant positive effects in isolated cat heart at an extracellular Ca2+ concentration of 2.5 mM. D600 exerted less of a depressant effect on contractility in rat than in cat heart at concentrations of 10(-6)--10(-7) M. The data suggest that 1) in contrast to results in cat heart, the positive inotropic effect of hyperosmolality in isolated rat cardiac muscle is apparent only when extracellular calcium concentration is reduced; 2) the inotropic effect of paired pacing in rat heart is greatest at low Ca2+ levels, but persists to a lesser degree at extracellular calcium concentrations of 2.5 mM; and 3) D600-inhibitable calcium channels appear to be relatively less important in the maintenance of cardiac contractility in rat than in cat cardiac muscle.

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