Comparative Studies on Rabbit Corpus Cavernosal Contraction and Relaxation. An In Vitro Study

ABSTRACT: Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators including nitric oxide. The specific aim of the current study was to determine the relative contribution of nitric oxide, adrenergic, purinergic, and cholinergic stimulation in the relaxant response to field stimulation. The results demonstrate that virtually all of the inhibitory effects of field‐stimulated relaxation could be explained by the release of nitric oxide. l‐NAME (l‐NG‐nitro arginine methyl ester, a competitive inhibitor of NO synthase) reduced field‐stimulated relaxation by over 95% at all frequencies. Neither atropine nor propranolol (or the combination of the two) had any significant effect on field‐stimulated relaxation. l‐NAME blocked both field‐stimulated relaxation and bethanechol‐stimulated relaxation. However, methylene blue (a guanyl cyclase inhibitor) was significantly more potent at blocking bethanechol‐stimulated relaxation than field‐stimulated relaxation. Neither l‐NAME nor methylene blue had any effect on nitroprusside (a direct liberator of NO) nor ATP‐stimulated relaxation. Isoproterenol had only a minor inhibitory effect on phenylephrine‐contracted tissue. These data suggest that 1) Methylene blue, which inhibits guanyl cyclase, is a relatively poor inhibitor of field‐stimulated relaxation. 2) l‐NAME is a potent inhibitor of NO synthesis and can in a dose‐dependent fashion inhibit over 95% of field‐stimulated relaxation. 3) Equipotent relaxation of corporal smooth muscle can be effected through pharmacologic stimulation with ATP (2 mM), nitroprusside (200 μM), and field stimulation (32 Hz). 4) If purinergic neurotransmission participates in physiologic erection, it does so by a mechanism independent of the l‐Arginine‐NO cGMP pathway.