Diamide: positive inotropic effect in isolated atria and inhibition of Na+/Ca2+ exchange in cardiomyocytes.

Summary The influence of frequency of stimulation and external calcium on the positive inotropic response of guinea-pig left atria to diamide and the inhibitory action on Na + /Ca 2+ exchange activity of rat cardiomyocytes by this oxidant of sulphhydryl groups have been investigated. Diamide (50–500 μ m ) induces a concentration-dependent positive inotropic effect which is more pronounced when atria are driven at 1.0 Hz rather than at 0.5 and 0.1 Hz, and are bathed in 2.72 m m rather than in 1.36 m m external calcium. A decrease in the positive inotropic effect at 35°C with respect to 29°C is also observed. In addition, diamide in positive inotropic concentrations (100–300 μ m ) significantly reduces Na + /Ca 2+ exchange activity and cytoplasmic glutathione levels in adult rat cardiomyocytes. The thiol reducing agent dithiothreitol either reverses or prevents diamide effects both in isolated atria and cardiomyocytes, suggesting that the actions of diamide are correlated to its property to oxidize sulphhydryl groups to disulphides. In view of the functional importance of Na + /Ca 2+ exchange in myocardial contractility, it is proposed that diamide may increase the heart force of contraction by an inhibition of the sarcolemmal Na + /Ca 2+ exchange activity.