Lactate accumulation in isolated hypoxic rat ventricular myocardium: effect of different modulators of the cyclic GMP system.

Abstract

Different agents which are known to increase tissue levels of cyclic guanosine 3':5'-monophosphate (cGMP), were found to decrease the lactate accumulation induced by hypoxia in isolated, non-beating rat myocardium from the right ventricle. One microM sodium nitroprusside increased the intracellular cGMP content 4 times during hypoxic conditions, and after 5 min. of hypoxia the intracellular lactate accumulation decreased by about 20%. 0.1 microM atrial natriuretic peptide increased cGMP 10 times during hypoxic conditions and decreased the lactate accumulation by about 40%. The reduction in lactate accumulation was mimicked by 1 mM 8-Br-cGMP and by Zaprinast (10 microM), a selective inhibitor of cGMP phosphodiesterase, which reduced lactate accumulation by 60% and 45%, respectively. Glyceryl trinitrate (1 nM and 1 microM) caused a slight increase in lactate accumulation both during normooxic and hypoxic conditions, but had no effect on tissue levels of cGMP. In conclusion, the results indicate that cyclic GMP reduces lactate accumulation in hypoxic, non-beating rat heart ventricular muscle and suggests that atrial natriuretic peptide, which is released from atrial tissue, may have beneficial metabolic effects on the heart.