title: Azelnidipine, a new calcium channel blocker, promotes skin wound healing in diabetic rats.
abstract: OBJECTIVE
  Impaired wound healing in diabetes is associated with decreased nitric oxide (NO) bioavailability in wound tissue. We hypothesized azelnidipine (AZL), a new calcium channel blocker with antioxidant properties, would enhance wound healing in streptozotocin-induced diabetic rats by restoring NO synthesis.
  
  
  METHODS
  Twelve male rats were taken as non-diabetic group. Twenty four rats were taken and caused to be diabetic by a single streptozotocin injection. Diabetic rats were divided randomly to two groups: control and treatment. Half of non-diabetic and also diabetic rats (in each group of control and treatment) randomly served as excisional-wound model and the other half as nitrite-measurement model. Six weeks after causing diabetes, the excisional wound model underwent dorsal full-thickness excisional wounds (1 × 1 cm). After wound healing completion, full-thickness skin samples (1 × 1 cm) were taken from the wound sites for evaluation of stereological parameters. The nitrite-measurement model (6 wk after causing diabetes) underwent insertion of subcutaneous polyvinyl alcohol sponges in dorsum. The rats were killed 2 wk post-wounding, and wound fluid was analyzed. In the study, after wounding, the treatment groups were gavaged with AZL (3 mg/kg/d) and control and non-diabetic groups with AZL vehicle till euthanasia.
  
  
  RESULTS
  AZL accelerated wound healing rate and also improved wound fluid NO level toward normal value in diabetic rats. Volume density of collagen fibers, numerical density of fibroblasts, and length density of vessels were increased in AZL-treated rats compared with control group.
  
  
  CONCLUSIONS
  AZL administration promotes diabetic wound healing by stimulating NO production and enhancing histologic processes central to normal wound healing.
authors.affiliation: Student Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Bagheri
authors.forename: Behnam Moein
authors.initials: BM
authors.lastname: Jahromi
authors.forename: Hossein
authors.initials: H
authors.lastname: Mirkhani
authors.forename: Zhabiz
authors.initials: Z
authors.lastname: Solhjou
authors.forename: Ali
authors.initials: A
authors.lastname: Noorafshan
authors.forename: Ali
authors.initials: A
authors.lastname: Zamani
authors.forename: Zahra
authors.initials: Z
authors.lastname: Amirghofran
mesh_terms: D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009573:Nitrites; D009569:Nitric Oxide; D001383:Azetidinecarboxylic Acid; D013311:Streptozocin; C061679:azelnidipine