Endothelin is a novel, potent, endogenous vasoconstrictor derived predominantly from endothelium and macrophages. Release of endothelin-1 (ET-1) into biological fluids was determined by radioimmunoassay in pigs undergoing either a hemorrhagic (3 h) or superior mesenteric artery (SMA) occlusion (5 h) shock followed by reperfusion (90 min) or a control group which was observed for 8 h. After surgery, there was a significant increase in ET-1 in jugular and carotid plasma, lymph, and ascitic fluid in all three models. The portal plasma ET-1 level was significantly increased (p .05, assessed by the Spearman rank coefficient rho;) in both shock models, but no significant increase was noted in the control group. In the SMA occlusion shock model, four pigs died within 30 min of reperfusion, and these animals had a much higher level of portal ET-1 (22.3 plusmn; 5.5 fmol/mL) than the two pigs that were alive by the end of the observation period (11.5 plusmn; 1.3 fmol/mL). Reperfusion in the SMA occlusion shock model induced a critical form of circulatory shock characterized by hypotension, decreased cardiac output, and decreased left and right ventricular stroke work index, and death occurred usually within 90 min. Reperfusion of the shed blood in the hemorrhagic shock model almost normalized the hemodynamic derangements caused by the hypovolemia (with the exception of RVSWI), and the portal plasma and ascitic ET-1 levels decreased. These results indicate that ET-1 is released from the gut in response to both general hypoperfusion and selective intestinal ischemia and reperfusion. We hypothesize that the extremely high portal ET-1 levels during reperfusion in the SMA occlusion shock model may contribute to the circulatory collapse and early death.
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