Abstract
Angiotensin-converting enzyme inhibitors have different effects on the cardiovascular system. The aim of this study was to investigate the effect of enalapril on skeletal muscle angiogenesis in diabetic and diabetic hind limb ischemic rats. We studied 24 male diabetic rats (induced by streptozotocin, 55 mg/kg, ip) divided into four groups. Groups 1 and 2 were diabetic sham (surgical procedure without femoral artery ligation). Groups 3 and 4 were diabetic animals subjected to induced hind limb ischemia. Groups 2 and 4 received enalapril (15 mg/kg/day, i.p) and groups 1 and 3 received an equal volume of saline. After 21 days, capillary density, capillary to fiber (cap/fib) ratio and serum concentrations of nitric oxide (NO), Vascular Endothelial Growth Factor (VEGF) and soluble VEGF Receptor-1 (sVEGF-R1) were evaluated. Enalapril significantly increased serum NO and VEGF concentrations and reduced serum sVEGF-R1 concentrations in diabetic sham and hind limb ischemic rats (p<0.05). Administration of enalapril significantly increased capillary density and cap/fib ratio in diabetic sham and hind limb ischemic animals compared with nontreated groups (p<0.05). Enalapril restores skeletal muscle angiogenesis in diabetic hind limb ischemia and can be considered for the prevention and treatment of peripheral artery disease in diabetic subjects.
Highlights
Peripheral artery disease is a major cause of morbidity and mortality in developed countries[1]
Peripheral artery disease and alteration in skeletal muscle microvasculature in the course of diabetes leads to tissue ischemia which may result in ulceration and amputation of the lower extremities[4,5]
The treatment of diabetic rats with enalapril did not cause any significant changes in body weight or blood glucose concentrations compared to controls (p>0.05)
Summary
Peripheral artery disease is a major cause of morbidity and mortality in developed countries[1]. Diabetes is one of the most important risk factors for the development of peripheral vascular disease[2]. For this reason, therapeutic angiogenesis is one approach to improving tissue perfusion and clinical outcome in diabetic subjects. Altered angiogenesis in diabetic states have been demonstrated in experimental and clinical studies. Peripheral artery disease and alteration in skeletal muscle microvasculature in the course of diabetes leads to tissue ischemia which may result in ulceration and amputation of the lower extremities[4,5]. The aim of this study was to investigate the effect of enalapril on skeletal muscle angiogenesis in diabetic and diabetic hind limb ischemic rats
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