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


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.
Bivalacqua
T J
TJ
Departments of Urology and Pharmacology, Tulane University Medical School, New Orleans, Louisiana, USA.
Diner
E K
EK
Novak
T E
TE
Vohra
Y
Y
Sikka
S C
SC
Champion
H C
HC
Kadowitz
P J
PJ
Hellstrom
W J
WJ
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010410:Penile Erection / Q000502:physiology*; D010411:Penile Induration / Q000473:pathology / Q000503:physiopathology*; D010413:Penis / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat