Role of endothelin in the circulatory changes associated with small bowel strangulation obstruction in pigs: Effects of the endothelin receptor antagonist bosentan

Background. We have previously shown that experimental strangulation obstruction leads to increased release and concentration of endothelin-1 (ET-1) in venous blood from the strangulated bowel loop. The present study focuses on the microcirculatory effects of the released ET-1 in strangulation obstruction. Methods. In anesthetized pigs strangulation obstruction was induced by increasing pressure in a baby pressure gasket placed around a loop of ileum until venous pressure reached 45 mm Hg. The pigs were randomly allocated into two groups. The nonselective ETA/ETB antagonist bosentan was administered intravenously (5 mg kg(-1)) to eight pigs (bosentan group) 30 min before strangulation, which was maintained for 90 min. Another eight pigs were treated in same manner except for the bosentan injection (control group). Results. The concentration of ET in arterial and intestinal venous blood increased markedly after intravenous administration of bosentan. Intravenous infusion of bosentan was followed by a reduction in systemic arterial blood pressure. Bosentan reduced vascular resistance and increased blood flow in the normal intestinal mucosa. It also reduced muscularis blood how in the beginning of the experiment. In strangulated small bowel bosentan inhibited the increase in vascular resistance usually caused by strangulation obstruction. Muscularis blood how in strangulated small bowel was not affected by bosentan. Conclusion. Endothelin is involved in the normal regulation of arterial blood pressure. The increase in vascular resistance associated with strangulation obstruction is caused mainly by locally released endothelin. (C) 2001 Academic Press.