Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats

• Published in: Physiological research Vol. 57; no. 3; pp. 491 - 494
• Main Authors: Kristová, V, Líšková, S, Sotníková, R, Vojtko, R, Kurtanský, A
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 01-01-2008
• Subjects: Acetylcholine - pharmacology; Animals; Blood Glucose - drug effects; Blood vessels; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetic Angiopathies - physiopathology; Diabetic Angiopathies - prevention & control; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Glycosaminoglycans - pharmacology; Hyperglycemia; Hypoglycemic Agents - pharmacology; Male; Nitric oxide; Rats; Rats, Wistar; Rodents; Time Factors; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.931506

Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.