Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collagen in wounds in mice.
OBJECTIVE
To investigate the effect of systemic inhibition of nitric oxide (NO) synthesis in wounds on collagen accumulation.


METHODS
Randomised experimental study.


METHODS
Teaching hospital, USA.


METHODS
240 Balb/C mice divided into groups of 10 animals each.


METHODS
Polyvinyl alcohol sponges were inserted subcutaneously through a dorsal skin incision. Beginning on the day of wounding, N omega-nitro-L-arginine-methylester (L-NAME), NG-L-monomethyl-arginine (L-NMMA), aminoguanidine hemisulphate (AGU), and S-methyl isothiouronium (MITU) were given orally or intraperitoneally. The mice were killed 10 days later.


METHODS
Nitrite and nitrate concentrations, both stable end products of NO, were measured in wound fluid. Sponge hydroxyproline content was assayed as an index of reparative collagen deposition.


RESULTS
NOS inhibitors given orally in the drinking water or by daily intraperitoneal injection had no effect on wound nitrite/nitrate concentrations or deposition of collagen in wounds. When given continuously through intraperitoneally-placed osmotic pumps, AGU (500 mg/kg/day) (p < 0.001) and MITU (p < 0.01) significantly reduced wound fluid nitrite/nitrate concentrations in a dose dependent manner. Inhibition of wound nitric oxide synthase by 500 mg AGU/kg/day and 100 mg MITU/kg/day was paralleled by lowered accumulation of collagen in wounds (p < 0.01).


CONCLUSIONS
NO is beneficial in wound healing.
Schäffer
M R
MR
Department of Surgery, University Hospital of Tübingen, Germany.
Tantry
U
U
Thornton
F J
FJ
Barbul
A
A
D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D011897:Random Allocation; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D003094:Collagen; D019001:Nitric Oxide Synthase