Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle

Field stimulation of the non-adrenergic, non-cholinergic inhibitory nerves to the bovine isolated retractor penis muscle evoked a relaxation that was preceded by a rise in the tissue content of cyclic GMP. There was no change in the content of cyclic AMP. The selective cyclic GMP phosphodiesterase inhibitor, 2-o- propoxyphenyl -8- azapurin -6-one (M&B 22948), elevated the tissue's cyclic GMP content, and potentiated both the relaxation and the rise in cyclic GMP produced by inhibitory nerve stimulation. Sodium nitroprusside and an inhibitory factor extracted from the bovine retractor penis muscle mimicked the effects of inhibitory nerve stimulation in that they each produced relaxation associated with a selective rise in cyclic GMP concentration. Haemoglobin (in the form of erythrocyte haemolysate) and N- methylhydroxylamine , which are known to block guanylate cyclase, blocked the relaxation and the rise in cyclic GMP content produced by inhibitory nerve stimulation, inhibitory factor and sodium nitroprusside. Haemoglobin itself caused a rise in muscle tone and at the same time reduced the cyclic GMP content of the tissue. 8-Bromocyclic GMP, a permeant derivative of cyclic GMP, produced a relaxation of the muscle that, as expected, was not blocked by haemoglobin. Vasoactive intestinal polypeptide, prostaglandin E1 and forskolin each produced relaxation associated with a selective rise in cyclic AMP content. Their effects were not blocked by haemoglobin or N- methylhydroxylamine . It is concluded that inhibitory nerve stimulation in the bovine retractor penis muscle produces a relaxation that is mediated by cyclic GMP, although some substances relax the muscle without affecting cyclic GMP levels. The results are also compatible with the view that the extracts of muscle contain the inhibitory neurotransmitter.