A rat model of Peyronie's disease associated with a decrease in erectile activity and an increase in inducible nitric oxide synthase protein expression

Purpose: Our objective was to assess erectile function in saline-injected, transforming growth factor-beta 1 (TGF-beta 1)-injected, and surgical injur y rats after six weeks and to determine the role of nitric oxide in this ra t model of Peyronie's disease. Materials and Methods: Fifty-four adult male CD rats were divided into thre e groups: 1) saline-injected (0.1 ml.) into the tunica albuginea; 2) TGF-be ta 1 (0.5 mu g.) injected into the tunica albuginea; and 3) surgical injury to the tunica albuginea. All groups underwent electrical stimulation of th e cavernosal nerve and pharmacological stimulation with acetylcholine, an e ndothelium-dependent vasodilator, after six weeks. In a separate group of a nimals, aminoguanidine (5 mg./kg. i.v.), a specific iNOS inhibitor, was adm inistered and cavernosal nerve stimulation was performed. Cavernosal tissue was homogenized and constitutive and inducible NOS enzyme activity were me asured by L-arginine to L-citrulline conversion in the presence and absence of calcium after 2 days, 3 and 6 weeks in all three groups. Cross-sections of the rat penises were examined using Hart and trichrome stains. Results: Erectile function as measured by cavernosal nerve stimulation and acetylcholine injection was significantly lower (p < 0.05) in the TGF-beta 1-injected and surgical-injury rats when compared to the saline-injected ra ts. iNOS inhibition significantly increased (p < 0.05) erectile responses t o cavernosal nerve stimulation in the rat. iNOS was significantly higher (p < 0.05) and constitutive NOS was downregulated (p (0.05) in the corpus cav ernosum of the TGF-beta 1-injected and surgical-injury rats after 6 weeks. The TGF-beta 1-injected and surgical-injury rats exhibited thickening of th e tunica albuginea, fragmentation of the elastic fibers, and collagen thick ening around the neurovascular bundle. Conclusions: We have shown that erectile function is significantly lower in the TGF-beta 1-injected and surgical-injury rats after 6 weeks at a time w hen iNOS is upregulated and constitutive NOS is downregulated. Furthermore, iNOS inhibition causes a greater erectile response in the rat, suggesting that iNOS may alter the vascular tone in the penis. These data document a p ossible mechanism by which some men with Peyronie's disease suffer from ere ctile dysfunction.