Open AccessEffects of Selective Endothelin Receptor Antagonist on Vegf Signaling System in Diabetic Penis: A Possible Clinical Implication for Diabetes Induced Erectile Dysfunction
Author(s) -
Adil Maqbool,
Subrina Jesmin,
Chishimba Nathan Mowa,
Sayeeda Sultana,
Nobutake Shimojo,
Yujiro Matsuishi,
Takeru Shima,
Naoto Yamaguchi,
Takashi Miyauchi,
Satoru Kawano,
Masao Moroi
Publication year - 2021
Publication title -
cardiology and vascular research
Language(s) - English
Resource type - Journals
ISSN - 2639-8486
DOI - 10.33425/2639-8486.1096
Subject(s) - medicine , endocrinology , diabetes mellitus , erectile dysfunction , streptozotocin , antagonist , endothelin receptor , vascular endothelial growth factor , penis , enos , receptor antagonist , antagonism , endothelin receptor antagonist , endothelin 1 , saline , receptor , vegf receptors , nitric oxide , surgery , nitric oxide synthase
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.