ENDOTHELIAL DYSFUNCTION IN THE SPLANCHNIC CIRCULATION FOLLOWING ISCHEMIA AND REPERFUSION

Splanchnic artery occlusion (SAO) for 90 min followed by reperfusion results in a severe form of circulatory shock characterized by hypotension and death usually within 2 h. An early consequence of the reperfusion is a marked endothelial dysfunction in which vasorelaxation to endothelial dependent dilators (e.g., acetylcholine and A-23187) is impaired, but vasorelaxation to direct vasodilators (e.g., acidified NaNO2) is normal. Infusion of recombinant human superoxide dismutase (hSOD) shortly before reperfusion prevents most of the endothelial dysfunction, attenuates much of the hypotension, and improves survival. Alternatively, infusion of nitric oxide (NO) also protects in this lethal form of shock. Thus, inhibition of endothelium-derived relaxing factor (EDRF) is an important pathophysiologic event in SAO and reperfusion, and replacement of EDRF either by an NO donor (e.g., acidified NaNO2) or NO itself protects in this lethal model of circulatory shock.