ABSTRACT
To evaluate the protective role of bosentan (BOS), an endothelin-1 (ET-1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg-1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg-1 and 100 mg kg-1 , respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET-1, eNOS, iNOS, tumour necrosis factor (TNF)-α, ET-RA and ET-RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET-1, TNF-α and iNOS gene expressions increased, eNOS, ET-RA and ET-RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF-α expressions in a dose-dependent manner.
Subject(s)
Diabetes Mellitus, Experimental/complications , Endothelin Receptor Antagonists/therapeutic use , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Penile Erection/drug effects , Sulfonamides/therapeutic use , Animals , Apomorphine/pharmacology , Bosentan , Dopamine Agonists/pharmacology , Endothelin Receptor Antagonists/administration & dosage , Endothelin-1/metabolism , Humans , Male , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , Penis/blood supply , Penis/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Sulfonamides/administration & dosage , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: The aim of this study is to show the effect of a new mechanism on endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan can reverse diabetes-induced lung injury. METHODS: The rats (24 male) were separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM): Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50 mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The bosentan treatment was initiated immediately after the onset of STZ-induced diabetes and continued for 6 weeks. RESULTS: In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNF-α and TGF-ß gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression. CONCLUSIONS: In conclusion, increased endothelin levels in the lung associated with diabetes may be one cause of endothelial dysfunction, cytokine increase, and oxidant/antioxidant imbalance in the pathogenesis of complications that may develop during diabetes. With its multiple effects, bosentan therapy may be an effective option against complications that may develop in association with diabetes.
