Calcium and calcium slow channel antagonists on cyclic nucleotide levels in the isolated rat heart

An investigation has been carried out into the effects of extracellular calcium on cyclic nucleotide levels in rat ventricle. Increasing extracellular calcium, over the range which directly affected contractility, produced a concentration related increase in the level of cyclic AMP. Positive correlations were found between extracellular calcium and cyclic AMP; and between cyclic AMP and isometrically developed tension. No reciprocal relationships were found for cyclic GMP over the same calcium concentration range. Increasing extracellular calcium above the maximal inotropic concentration did not produce a further increase in cyclic AMP, although increases in cyclic GMP were noted. Calcium slow channel antagonists, nifedipine and manganese both depressed developed tension at the concentrations used, but this effect was not associated with any significant change in cyclic nucleotide levels. Verapamil depressed developed tension and cyclic AMP levels but the effect on cyclic AMP was not concentration related. No calcium slow channel antagonist significantly affected cyclic GMP levels. In electrically paced hearts, increasing rate of stimulation depressed developed tension but had no significant effect on cyclic AMP.