title: Limbs' postischemic revascularization is not improved by losartan treatment in diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: A
authors: A
authors: Fallahzadeh
authors: M
authors: M
authors: Khazaei
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D019808:Losartan