Nitric oxide inhibits wound collagen synthesis

Nitric oxide (NO) is a messenger molecule which regulates many physiologica l functions like immunity, vascular tone and serves as a neurotransmitter. Although it is known to participate in healing process, its role in collage n synthesis is not clear. Therefore, the present investigation was done to study the role of NO in wound collagen synthesis. Rats received full thickn ess, circular (8 mm), transdermal wounds which were treated with NO release r, sodium nitroprusside (SNP, 0.001 100 mu M) topically for 5 days. Wound c ollagen content estimated in terms of hydroxyproline (HP) and confirmed his tochemically was decreased significantly by all SNP doses. L-Arginine, a su bstrate for nitric oxide synthase (NOS) when applied topically decreased co llagen content of the wounded tissues. N-Nitro-L-arginine methyl ester (L-N AME), a competitive inhibitor of NOS, increased wound collagen content sign ificantly as compared to untreated and SNP treated animal wounds when admin istered intraperitoneally at the doses 3, 10 and 30 mg/kg. Furthermore, his tological findings also demonstrated laying down of thick collagen bundles and proliferation of fibroblasts together with prominent angiogenesis in L- NAME treated wound tissues as compared to untreated and SNP treated tissues . N-nitro-D-arginine methyl ester, an inactive isomer, was found to have no effect on wound collagen levels. When L-arginine was administered in L-NAM E pretreated rats, it significantly elevated wound HP content. The results indicate that NO plays an important role in regulating the collagen biosynt hesis in skin model of a healing wound.