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 w as to ascertain the degree to which cyclic GMP is involved in these interac tions. 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 guany late cyclase inhibitors Methylene Blue (MB) and LY83583; 100 mu M MB led to increases in resting tension which were antagonized by indomethacin, nifed ipine, phentolamine, but not superoxide dismutase (SOD). Contractile respon ses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD, Pyroga llol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endot helium-dependant relaxation in RCC results in activation of soluble guanyla te cyclase and release of a stable endothelium derived contracting factor(s ), which is likely to be a constrictor prostanoid(s), Tonic production of c GMP in RCC inhibits the presynaptic release and contractile effects of NA a nd can be modulated by cyclo-oxygenase inhibition, demonstrating the import ant interaction and functional antagonism between cGMP and prostaglandins i n the control of CSM tone. (C) 2000 Harcourt Publishers Ltd.