Bosentan Ameliorates Diabetic Angiopathy and Nephropathy in Streptozotocin-Induced Diabetic Model in Albino Rats

Abstract

Angiopathy and nephropathy are serious problems encountered in management of diabetes mellitus. Angiotensin II (AII) and endothelins (ETs) receptors play an important role in the pathogenesis of diabetic complications. The purpose of this study was to investigate the possible renoprotective and antiangiopathic effects of the non-selective endothelin (ET) receptor blocker bosentan in type 1 diabetic model of albino wister rats. These rats were divided into four groups ( each group , N= 12 rats): control group (1), control group (2) treated with bosentan (50 mg/kg/day), untreated diabetic group (3) and diabetic group (4) treated with bosentan. Induction of type 1 diabetes mellitus in tested rats was performed by a single injection, in the tail vein, of 35 mg/kg streptozotozin after overnight fast. Treatment with bosentan was continued for 12 weeks during which the 24h urine volume, urinary albumin content, urine and plasma levels of creatinine as well as mean non-invasive blood pressure (mean BP) were assessed at the end of each 4 weeks. At the end of the 12th week rats were sacrificed then the thoracic aortae were dissected for assessment of the vasorelaxant effect of acetylcholine. Diabetic rats showed hyperglycemia, polyuria, albuminuria, elevated mean BP, reduced response to vasorelaxant effect of ACh. Bosentan significantly reduced albuminuria and lowered elevated mean BP. In addition the drug restored the normal values of creatinine clearance and improved vascular reactivity to ACh. The present study suggested a possible renoprotective and aortic vasorelaxant effects by bosentan without a significant effect on the control of blood glucose. The results of the present study was directed towards a possible role of bosentan, as a drug acting on Endothelin receptors, in the improvement of diabetic angiopathy and nephropathy.