Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie's-like condition in the rat

Peyronie's disease is an idiopathic, localized connective tissue disorder o f the penis, involving the tunica albuginea of the corpus cavernosum and ad jacent areolar space. Current proposals as to the origin of Peyronie's dise ase suggest that fibrosis and collagen changes of the tunica are the result of an inflammatory process following vascular trauma. Our laboratory and o ther investigators have recently proposed an animal model for the study of Peyronie's disease. When transforming growth factor-beta1 (TGF-beta1) was i njected into the rat tunica albuginea, tissue fibrosis was observed at 6 we eks. Therefore, our aim was to assess arginase II, endothelial and inducibl e nitric oxide synthase isoforms, and nitrotyrosine levels-all factors invo lved in inflammatory reactions-in the cavernosal tissue of saline-injected and TGF-beta1-injected rats after 6 weeks in order to evaluate the roles th ese enzymes may play in the induction of a Peyronie's-like condition in the rat. To examine the expression of endothelial nitric oxide synthase (eNOS) , iNOS, and arginase II protein, and mRNA in the corpus cavernosum, immunob lot analysis, and reverse transcriptase-polymerase chain reaction were perf ormed. We also determined immunohistochemically the expression of nitrotyro sine, a marker of peroxynitrite formation, in the rat penis. After 6 weeks, iNOS protein and gene expression was up-regulated and eNOS protein and gen e expression was down-regulated in the corpora cavernosa of the TGF-beta1-i njected penises. Furthermore, arginase II protein expression as well as imm unohistochemical localization of nitrotyrosine was significantly higher in the TGF-beta1-injected corpora cavernosa. These results suggest that iNOS i s the key control element for peroxynitrite formation, arginase ii expressi on, and eNOS down-regulation in the induction of a Peyronie's-like conditio n in therapy.