Combination of phentolamine and L-arginine or sildenafil synergistically improves neurogenic relaxation of rabbit corpus cavernosum smooth muscle

Objectives. To analyze the effects of combining an alpha-adrenergic recepto r antagonist, phentolamine, with an enhancer of the nitric oxide/cyclic gua nosine monophosphate pathway (L-arginine or sildenafil) on neurogenic relax ations of rabbit corpus cavernosum (RCC). Methods. Studies were performed on isolated RCC tissue in organ chambers. T ransmural electrical stimulation (TES) was applied at increasing frequencie s (.5 to 6 Hz) on endothelin-contracted RCC strips, and the responses were evaluated. Results, The activation of alpha(2)-adrenergic receptors with UK 14304 (0.3 muM) significantly inhibited the relaxation induced by TES in RCC strips i n which adrenergic neurotransmission was blocked with guanethidine (10 muM) . The relaxant responses produced by TES application on RCC strips without guanethidine were not significantly affected by the treatment with L-argini ne or sildenafil but were significantly augmented by phentolamine (2.7-fold increase in maximum relaxation). Furthermore, the combinations of phentola mine with L-arginine or sildenafil markedly increased the relaxations evoke d by the application of TES in RCC tissue, significantly more than those ob tained in the presence of phentolamine alone (4.5 or 4.7-fold increase of m aximum relaxation, respectively). Conclusions, Our results demonstrated a synergistic interaction between the alpha-adrenergic blockade and the potentiation of the nitric oxide/cyclic guanosine monophosphate pathway to increase neurogenic relaxation of trabec ular smooth muscle relaxation. This fact suggests that the combination of a lpha-adrenergic receptor blockade with L-arginine or sildenafil could repre sent a therapeutic advantage in the treatment of erectile dysfunction. UROL OGY 57: 585-589, 2001. (C) 2001, Elsevier Science Inc.