Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic,noncholinergic mechanism

The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evok ed nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro, Stimulation of nonadrenergic, noncholinergic neuron s of the rabbit corpus cavernosum elicited frequency-related relaxation tha t was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ tan inhibitor of guanylate cyclase), Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of r abbit corpus cavernosum suggesting that neuronal release of NO mediates rel axation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxati on of the rabbit corpus cavernosum. Prazosin (30 muM) and yohimbine (30 muM ) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholine rgic rabbit penile smooth muscle relaxation, suggesting that phentolamine r elaxes rabbit corpus cavernosum independent of a-adrenergic receptor blocka de. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME s ignificantly-attenuated electrical field stimulation produced relaxations t o phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabb it corpus cavernosum by activating NO synthase, The data suggest that phent olamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of cr-adren ergic receptor blockade.