8,10,11,15,25–27 During this period of neuropraxia, there is absence of spontaneous nocturnal erections that leads to the loss of production of nitric oxide (NO), both by the neuronal isoform of nitric oxide synthase (nNOS) via the nerves themselves and the inducible isoform of nitric oxide synthase (iNOS) via the cavernosal smooth muscle cells, due to loss of Inhibitors,research,lifescience,medical tissue

oxygenation produced by tumescence.11,14,15 These changes induce the production of proapoptotic factors and profibrotic factors within the corpora cavernosa.11 The loss of nocturnal erections or damage to the accessory pudendal arteries during RP contributes to prolonged periods of penile smooth muscle hypoxia/ischemia, which leads to the production of transforming growth factor-β1 (TGF-β1) and TGF-β1-dependent endothelin-1 (ET-1).25 ET-1 has been shown to be a potent constrictor of penile smooth muscle and a profibrotic peptide, which induces collagen deposition in cavernosal tissue.25 Daley and associates showed that the production of prostaglandin E-1 (PGE-1) suppressed Inhibitors,research,lifescience,medical TGF-β1-induced collagen accumulation in cavernosal muscle cells.28 Moreland and colleagues also showed that the addition of PGE-1 to cavernosal cultures suppressed TGF-β1-induced collagen synthesis.29 Thereby, Inhibitors,research,lifescience,medical loss of erections due to decreased vascular inflow or loss of NO-induced tumescence contributes

to the loss of PGE-1 feedback control on TGF-β1 production and perpetuates penile fibrosis, apoptosis, and programmed cell death.25 Some studies have shown in rats after bilateral neurectomy and in men after RP that smooth muscle degradation is followed by Selleck PF 4708671 increased levels of collagen type I and collagen type III deposition.10 User and coauthors30 demonstrated loss of penile wet weight in rats that underwent both bilateral and unilateral Inhibitors,research,lifescience,medical cavernous nerve transection. Their data show that the average penile weight reduction was 13.6%, with the greatest reduction of 17.4% seen in the bilateral cavernous neurotomy group on postoperative day 60 (P < .005). A statistically

significant decrease in penile wet weight of 10.5% was seen at the 60-day point in the unilateral denervated penes (P = .029). They Inhibitors,research,lifescience,medical also demonstrated a statistically Sodium butyrate significant decrease in DNA content in the bilaterally denervated penes (P < .05). Klein and associates showed increased DNA fragmentation and elevation of sulfated glycoprotein-2 (SGP-2) in the erectile tissue of denervated rat penes, which are both markers of apoptosis.27 Conversely, Müller and colleagues demonstrated the early use of hyperbaric oxygen therapy in rat cavernous nerve injury model improved erectile function recovery, endothelial nitric oxide synthase (eNOS), and nerve growth factor expression.31 The development of penile fibrosis leads to the long-term development of corporal veno-occlusive dysfunction/venous leakage because of the loss of cavernosal smooth muscle cell mass to adequately compress the subtunical veins during tumescence.