Effects of Selective Endothelin Receptor Antagonist on Vegf Signaling System in Diabetic Penis: A Possible Clinical Implication for Diabetes Induced Erectile Dysfunction

Abstract

Erectile dysfunction (ED) affects around 50 percent of male diabetic patients due to vascular and neuropathic complications arising from diabetes. Vascular endothelial growth factor (VEGF) has been extensively investigated for its pathogenic relevance in various diabetes complications, and we have already noted that VEGF signaling is significantly reduced at the insulin-resistant stage in the penis of type II diabetic rat model. The present research used a three-week streptozotocin (STZ)-induced diabetic (DM) rat model to determine the expression of VEGF with NO mechanism in penile tissue and subsequently investigated its impact endothelin antagonism on these shifts. Citrate saline vehicle or STZ (65 mg/kg IP) was administered to male Sprague-Dawley rats (weight 453 ± 23 g). Hyperglycemia confirmed diabetes, and then after 1 week of diabetes, animals were divided into receiving endothelin-A (ET-A) receptor antagonists (TA-0201, 1 mg/kg) or saline by osmotic minipump for 2 weeks and then sacrificed. Significantly improved glucose levels in DM rats (405 ± 103 mg/dL) relative to non-DM rats (120 ± 8 mg/dL) and higher local ET-1 levels in DM penis by 20% are observed. A 30 percent decline in penile tissue expression of VEGF was observed in DM rats and improved by an antagonist with ET. Penile NO and eNOS levels in DM rats decreased, while ET-A receptor antagonist significantly increased. Therefore, we infer that ET antagonism seemed able to restore the down-regulated VEGF and was possibly efficient in restoring the decreased levels of NO and eNOS in DM.