Nitric oxide enhances experimental wound healing in diabetes.
BACKGROUND
Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes.


METHODS
Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed.


RESULTS
OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes.


CONCLUSIONS
The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.
Witte
M B
MB
Departments of Surgery, Sinai Hospital of Baltimore and the Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. maria.witte@uni-tuebingen.de
Kiyama
T
T
Barbul
A
A
D000818:Animals; D015152:Blotting, Northern; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental; D006909:Hydroxyproline / Q000378:metabolism; D008264:Macrophages; D008981:Molsidomine / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015503:Surgical Sponges; D014665:Vasodilator Agents / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D014665:Vasodilator Agents; D009569:Nitric Oxide; D008981:Molsidomine; D006909:Hydroxyproline