Effect of ischaemia on endothelium-dependent vasodilatation in the isolated rat superior mesenteric artery.

The isolated perfused rat superior mesenteric artery preparation was used to determine whether endothelium-dependent vasodilatation occurs in this vessel, and to test whether impairment of this function may contribute to post-ischaemic mesenteric vasospasm. It was found that vessels preconstricted with noradrenaline responded to optimal concentrations of acetylcholine (3 X 10(-5) M), ADP (2 X 10(-5) M) and to isolated homologous platelets (500,000/mm3) with an 84%, 85% and 37% decrease in mean perfusion resistance, respectively. In preparations treated with collagenase to denude the vessels of endothelium there was a significantly diminished response to acetylcholine and ADP (24% & 23% decrease in resistance, respectively). Platelets, on the other hand, caused a further 34% increase in resistance. A model of mesenteric ischaemia was produced by interrupting perfusate flow through the preparation for intervals of 1 to 4 h. This was associated with morphological evidence of endothelial cell damage and with a progressive decline in the responsiveness to acetylcholine and ADP. After 1 h there was also a significant reduction in the response to platelets. With intervals of ischaemia longer than 2 h platelets caused only further constriction which could be inhibited by the serotonin antagonist, methysergide. This study suggests that an altered response of the endothelium to platelet-derived vasoactive substances may contribute to the post-ischaemic vasospasm encountered during reperfusion.