Central modulation of the NO/cGMP pathway affects the MPOA-induced intracavernous pressure response

Alterations in the nitric oxide (NO)/ cGMP levels in hypothalamic nuclei, i ncluding the medial preoptic area (MPOA), regulate critical aspects of sexu al behavior and penile reflexes. However, the effects of altered central ne rvous system (CNS) NO/cGMP levels at the end organ level, that is, on the m agnitude/quality of the erection so achieved [intracavernous pressure (ICP) response], has yet to be evaluated. The goal of this report was to evaluat e the effects of intrathecal administration of modulators of NO and cGMP le vels on ICP responses to stimulation of the MPOA and cavernous nerve in rat s in vivo. In all cases, intrathecal administration of compounds that incre ase and decrease cGMP and NO levels, respectively, was associated with corr esponding increases and decreases in the MPOA-stimulated ICP response. Spec ifically, sodium nitroprusside (SNP), 8-bromo-cGMP, and sildenafil increase d the MPOA-stimulated ICP response, whereas N-omega-nitro-L-arginine methyl ester reduced it. None of the intrathecal treatments had detectable effect s on blood pressure or the cavernous nerve-stimulated ICP response, althoug h intravenous sildenafil increased the latter. These data clearly indicate that intrathecal drug administration affects central and not peripheral neu ral mechanisms and, moreover, documents that CNS NO/cGMP levels can affect erectile capacity per se (i.e., ICP) in the rat model.