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

Abstract

Purpose: Our objective was to assess erectile function in saline-injected, transforming growth factor-beta 1 (TGF-beta1)-injected, and surgical injury rats after six weeks and to determine the role of nitric oxide in this rat model of Peyronie's disease.

Materials and methods: Fifty-four adult male CD rats were divided into three groups: 1) saline-injected (0.1 ml.) into the tunica albuginea; 2) TGF-beta1 (0.5 microgram.) injected into the tunica albuginea; and 3) surgical injury to the tunica albuginea. All groups underwent electrical stimulation of the cavernosal nerve and pharmacological stimulation with acetylcholine, an endothelium-dependent vasodilator, after six weeks. In a separate group of animals, aminoguanidine (5 mg./kg. i.v.), a specific iNOS inhibitor, was administered and cavernosal nerve stimulation was performed. Cavernosal tissue was homogenized and constitutive and inducible NOS enzyme activity were measured 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-beta1-injected and surgical-injury rats when compared to the saline-injected rats. iNOS inhibition significantly increased (p <0.05) erectile responses to cavernosal nerve stimulation in the rat. iNOS was significantly higher (p <0.05) and constitutive NOS was downregulated (p <0.05) in the corpus cavernosum of the TGF-beta1-injected and surgical-injury rats after 6 weeks. The TGF-beta1-injected and surgical-injury rats exhibited thickening of the tunica albuginea, fragmentation of the elastic fibers, and collagen thickening around the neurovascular bundle.

Conclusions: We have shown that erectile function is significantly lower in the TGF-beta1-injected and surgical-injury rats after 6 weeks at a time when 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 possible mechanism by which some men with Peyronie's disease suffer from erectile dysfunction.