Premium
Effects of endothelin antagonism on VEGF and NO levels in penile tissues in type 1 diabetic rat model
Author(s) -
Jesmin Subrina,
Mowa Chishimba,
Zaedi Sohel,
Sultana Sayeeda Nusrat,
Yamaguchi Naoto
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb349
Subject(s) - endocrinology , medicine , streptozotocin , vascular endothelial growth factor , antagonist , diabetes mellitus , endothelin receptor , saline , antagonism , receptor antagonist , endothelin 1 , penis , endothelin receptor antagonist , erectile dysfunction , receptor , vegf receptors , surgery
Erectile dysfunction (ED) affects about 50% of males with diabetes, possibly due to the vascular and neuropathic complications. The pathogenic significance of Vascular endothelial growth factor (VEGF) in different diabetic complications have been extensively documented and we have previously reported that its (VEGF) signaling is greatly diminished in the penis a type II diabetic rat model at the insulin‐resistant stage. In the present study, we used a rat model that was treated for three weeks with streptozotocin (STZ), a chemical that induces diabetes, in order to assess the expression patterns of VEGF and the NO system in penile tissue and the effects of endothelin antagonism on these changes. Male Sprague‐Dawley rats (weight, 450±26 g) were administered citrate saline vehicle or STZ (65 mg/kg IP). Diabetes was confirmed by hyperglycemia and after 1 week of diabetes, animals were either treated with endothelin‐A (ET‐A) receptor antagonist (TA‐0201, 1 mg/kg) or saline for 2 weeks by osmotic mini pump and then sacrificed. Levels of glucose levels in DM rats were found to increase significantly (405±103 mg/dL) compared to non‐DM rats (120±8 mg/dL) and ET‐1 levels in DM penis was found to be higher by 20%. A 30% decrease in VEGF levels was observed in penile tissue of DM rats and ET‐A antagonist did not attenuate the observed decrease in VEGF levels. Lastly, penile levels of NO and eNOS decreased in DM rats, but were almost restored back to normal by ET‐A receptor antagonist. We conclude that ET antagonism is not effective in restoring the down‐regulated levels of VEGF, but is effective in reversing the decreased levels of NO and eNOS in DM penis.