The effect of cyclic GMP on rabbit corporal smooth muscle tone and its modulation by cyclo-oxygenase products

Corporal smooth muscle (CSM) tone is maintained by a finite balance between relaxant and contractile neurotransmitters. The aim of these experiments was to ascertain the degree to which cyclic GMP is involved in these interactions. We also sought to elucidate the pharmacological mechanism of action of MB in rabbit corpus cavernosum (RCC), an important tool in nitric oxide research. Using an organ chamber technique, strips of RCC were treated with the guanylate cyclase inhibitors Methylene Blue (MB) and LY83583; 100 microM MB led to increases in resting tension which were antagonized by indomethacin, nifedipine, phentolamine, but not superoxide dismutase (SOD). Contractile responses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD. Pyrogallol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endothelium-dependent relaxation in RCC results in activation of soluble guanylate cyclase and release of a stable endothelium derived contracting factor(s), which is likely to be a constrictor prostanoid(s). Tonic production of cGMP in RCC inhibits the presynaptic release and contractile effects of NA and can be modulated by cyclo-oxygenase inhibition, demonstrating the important interaction and functional antagonism between cGMP and prostaglandins in the control of CSM tone.