We studied the effects of nitric oxide (NO) solution and acidified sodium nitrite (NaNO2), which produces NO, in splanchnic artery occlusion (SAO) shock in cats. NO is thought to be endothelium-derived relaxing factor (EDRF), a labile substance having several potentially valuable biological effects. Anesthetized cats subjected to total occlusion of the celiac, superior mesenteric, and inferior mesenteric arteries for 120 min, followed by reperfusion, usually died approximately 60 min after reperfusion. NO infusion significantly improved survival time in SAO-shock cats compared with those receiving vehicle (P less than 0.005). Administration of NO also attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (P less than 0.05), total amino-nitrogen (P less than 0.001), and of the cardiotoxic peptide, myocardial depressant factor (MDF) (P less than 0.001). SAO-shock cats treated with NaNO2 at pH 2.0 also exhibited lower plasma cathepsin D (P less than 0.001), amino-nitrogen (P less than 0.05), and MDF activities (P less than 0.01), and survival time was also significantly improved (P less than 0.02). The same dose of NaNO2 infused at pH 7.4 failed to exert any significant protective effect. These results indicate that NO exerts beneficial effects in SAO shock in cats and suggest that exogenously administered NO may be a potentially useful therapeutic agent in splanchnic ischemic shock, probably via a cytoprotective rather than a vasodilator effect.