Cyclic AMP and cyclic GMP may play opposing roles in influencing force of contraction in mammalian myocardium

Abstract

CYCLIC AMP and cyclic GMP have been suggested to play opposing regulatory roles in several biological systems1. Supporting evidence for the yin yang hypothesis of opposing biological regulation has been obtained in sympathetic ganglia2,3 and pyramidal neurones in the rat cerebral cortex4. In the mammalian heart, the role of cyclic AMP in mediating the positive inotropic response to catecholamines was advanced by the observation that the inotropic effect was preceded by an increase in cyclic AMP levels5. On the other hand, the levels of cyclic GMP were found to be increased after cholinergic stimulation6. In frog, oscillations of cyclic AMP7 and cyclic changes in the levels of cyclic AMP and cyclic GMP8 during the cardiac cycle have been reported. The importance of cyclic AMP for the inotropic effects of catecholamines was confirmed by the observation that the dibutyryl derivative of cyclic AMP exerted a positive inotropic effect in cat papillary muscles9 and in the isolated perfused hearts from rabbits, rats and guinea pigs10. I now report a direct negative inotropic effect of 8-Br-cyclic GMP on force of contraction (Fc) in rat auricles and papillary muscles from cats.

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