The role of nitric oxide in the pathogenesis of venous ulcers.

Chronic venous insufficiency frequently leads to ulceration. The exact pathophysiological mechanisms underlying the development of venous ulceration remain to be elucidated. One major etiological factor of the trophic changes is the phenomenon of leukocyte trapping. The aim of the study was to review the pathophysiological events culminating in venous ulceration, focusing primarily on the role of alterations in nitric oxide (NO) production. We establish the hypothesis that venous stasis in the microcirculation reduces the rate of shear stress on the endothelial cells, effectively resulting in a decrease in cellular levels of NO, a key event of enhanced adhesion molecule expression and subsequent massive neutrophil activation. A similar series of events is proposed to explain the ischemic-reperfusion tissue injury. Inducible NO (iNO) produced by the inflammatory cells causes free radical injury seen as a venous ulceration.