Limbs’ postischemic revascularization is not improved by losartan treatment in diabetic rats

Abstract

Most physiological actions of angiotensin II (Ang II) on cardiovascular system are mediated by angiotensin type 1 receptor (AT1R). Since peripheral artery disease is one of the most important complications of diabetes, in this study, we aimed to investigate the effect of losartan, an AT1R blocker, on skeletal muscle angiogenesis in diabetic hind limb ischemic rats. Twenty four male Wistar rats were randomly divided into four groups as follow: diabetic sham; diabetic sham + losartan (15 mg/kg/day); diabetic hindlimb ischemia; diabetic hindlimb ischemia + losartan. For induction of diabetes, streptozotocin was injected (55 mg/kg; i.p.). The animals were sacrificed after 21 days and the serum concentrations of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sFlt-1), nitric oxide (NO), capillary density, and capillary to fiber (cap⁄fib) ratio in ischemic legs were evaluated. The serum NO concentrations were significantly decreased, sFlt-1 concentrations increased, and VEGF concentrations did not significantly change after experiment in diabetic sham and diabetic hind limb ischemic rats. Administration of losartan did not induce significant changes in serum NO, sFlt-1, and VEGF concentrations (p>0.05). Capillary density and cap⁄fib ratio in ischemic leg of diabetic rats were not affected by losartan treatment (p>0.05). AT1R blocker, losartan, was not able to restore neovascularization in the ischemic leg of diabetic animals. Therefore, based on the present data, the losartan cannot be considered for treatment or prevention of peripheral artery disease in diabetic subjects.