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Radical prostatectomy (RP) is the most commonly employed curative intervention for the treatment of prostate cancer. However, due to the proximity of the cavernous nerves (CN) to the prostate, RP results in transient and/often permanent erectile dysfunction (ED). While the prevention of traction injuries during the RP is critical for the preservation of erectile function, several preclinical studies have demonstrated the beneficial effects of neuroprotective (or neuroregenerative) agents in mitigating neuronal injuries sustained during RP. The maintenance or restoration of erectile function after injury may be enhanced in the postoperative period by the stimulation of neurogenesis to protect and restore injured nerves from further deterioration. The present review aims to evaluate and summarize research of these treatment strategies as published in the National Library of Medicine (Pubmed) from 2000 to 2015. The keywords used for the search were ED, RP, CN injury, immunophilin ligands, neurotrophins and phosphodiesterase (PDE)5 inhibitors, and animal models. Current guidelines for treatment targeting CN recovery recommend the use of immunophilin ligands, neurotrophins, brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor, sonic hedgehog (Shh), Rho-kinase, PDE5 inhibitors, erythropoietin (EPO), hyperbaric oxygen, gene, stem cells, and triiodothyronine (T3) therapy. Additionally, this review identifies remaining gaps in general knowledge and recent updates recognizing the need for further preclinical and clinical trials.

Erectile dysfunction (ED) is a common, male sexual disorder that has a negative impact on the quality of life of men and their sexual partners. The prevalence of ED in diabetic men is ≥50%. Animal models provide a valuable perspective in the investigation of ED. Most basic science studies have utilized the rodent model of type 1 diabetes. However, an animal model for type 2 diabetes-associated ED requires verification. The streptozotocin (STZ) induced type 1 diabetic model has contributed to significant advancement in the study of ED. A Medline search using the keywords "diabetic animals and ED" was performed, and available peer-reviewed English articles between 2007-2013 were evaluated. The proposed mechanisms for developing ED in diabetics include: hyperglycemia, impaired nitric oxide (NO) synthesis, cyclic guanosine monophosphate (cGMP) pathway dysfunction, increased levels of reactive free-radicals, up-regulation of the RhoA/Rho-kinase pathway, and neuropathic damage. The current treatment regimen of diabetes-induced ED is multimodal. Modification of comorbidities and, specifically, rectifying the underlying hyperglycemia is vital to prevent or halt progression of the disease. Further research on the basic mechanisms of ED and additional studies using better animal models of ED associated with type 1 and 2 diabetes are needed. Preclinical studies using the diabetic animal model will likely provide further insight for intervention and prevention strategies for diabetic ED treatment.

Responses to the P2X-purinoceptor agonist alpha,beta-methylene-ATP (alpha,beta-MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of alpha,beta-MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was alpha,beta-MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > alpha,beta-MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to alpha,beta-MeATP was compared with responses to angiotensin II and U-46619. The P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid attenuated the pressor response to alpha,beta-MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to alpha,beta-MeATP were not altered by cyclooxygenase, alpha-adrenergic, or angiotensin AT(1) antagonists. These data show that alpha,beta-MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, alpha,beta-MeATP had modest pressor activity in the systemic bed, where it was 1,000-fold less potent than angiotensin II. These data suggest that responses to alpha,beta-MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed.