The conundrum of inducible nitric oxide synthase in chronic leg ulcers.

Nitric oxide (NO) is a potent biological mediator that can be produced in wounds by activation of inducible nitric oxide synthase (iNOS). Its presence appears to be beneficial to the healing process by promoting vasodilation and boosting both migration and synthetic activity of fibroblasts. Chronic leg ulcers differ from acute experimental wounds because the connective tissue and microvascularization of the ulcer bed are strikingly remodelled in chronic wounds. In addition, a bacterial critical colonization from the environment is also often present and deleterious. As such, NO release in leg ulcers may prove to be beneficial by improving the microvasculature and fibroblast functions, and by its antimicrobial effect. However, any excess in NO could become cytotoxic for keratinocytes, thus impeding re-epithelialization. Furthermore, chronic NO release could be involved in the cancerogenesis process leading to Marjolin ulcer. In conclusion, NO induced by environment factors mediates contrasted effects in wound healing that may be beneficial or detrimental for the patient.