title: Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.
abstract: BACKGROUND
  Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation.
  
  
  METHODS
  Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three.
  
  
  RESULTS
  After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice.
  
  
  CONCLUSIONS
  Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.
authors.affiliation: EA6309, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. adanigo87@gmail.com.
authors.forename: Aurore
authors.initials: A
authors.lastname: Danigo
authors.affiliation: EA3842, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. Mohamednasser@hotmail.fr.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Nasser
authors.affiliation: EA6309, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. flavienbessaguet@gmail.com.
authors.forename: Flavien
authors.initials: F
authors.lastname: Bessaguet
authors.affiliation: EA3842, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. james.javellaud@unilim.fr.
authors.forename: James
authors.initials: J
authors.lastname: Javellaud
authors.affiliation: EA3842, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. nicole.oudart@unilim.fr.
authors.forename: Nicole
authors.initials: N
authors.lastname: Oudart
authors.affiliation: EA3842, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. jean-michel.achard@unilim.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Achard
authors.affiliation: EA6309, School of Medecine and Pharmacy, University of Limoges, 87025, Limoges Cedex, France. claire.demiot@unilim.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Demiot
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D003668:Pressure Ulcer / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan