Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens

SMOOTH muscle tone seems to be primarily regulated by the concentration of free calcium in cytoplasm1,2. Several agents that cause smooth muscle contraction increase the tissue content of cyclic GMP with no significant change or only small reduction of the cyclic AMP concentration3–7. It has been suggested5–7 that cyclic GMP may be casually involved in the contractile response of smooth muscle and that this nucleotide may act as a comediator with calcium to promote contraction. Several observations, however, are not consistent with this assumption. Although increases both in tissue tonus1,2 and in the cyclic GMP level8–10 induced by hormones and neurotransmitters are generally dependent on the presence of extracellular calcium and seem to be secondary to increased influx of calcium into the cytoplasm, the correlation between these two calcium-dependent events is poor in various tissues10–16. On the basis of such observations, we have suggested that cyclic GMP may act as a negative feedback inhibitor of hormonally stimulated calcium influx into cytoplasm8,10,11. We have studied the effects of various agents on cyclic nucleotide levels in the ductus deferens of the rat, and report here that many smooth muscle relaxants, including sodium nitroprusside (SNP), increase cyclic GMP levels in the ductus deferens.