ENDOTHELIUM-INDEPENDENT PRESSOR EFFECT OF BIG ENDOTHELIN-1 AND ITS INHIBITION BY PHOSPHORAMIDON IN RAT MESENTERIC-ARTERY

We asked whether or not the endothelium plays a functional role in the conversion of big endothelin-1 to endothelin-I in the perfused rat me senteric artery. In endothelium-denuded preparations, big endothelin-1 produced a much more potent pressor effect than in intact preparation s. Phosphoramidon suppressed the big endothelin-1-induced pressor acti on without affecting the action of endothelin-1, irrespective of the p resence or absence of the endothelium. The amounts of immunoreactive-e ndothelin in the perfusate during perfusion of endothelium-denuded pre parations with big endothelin-1 were extremely low compared with those observed in intact preparations and were not significantly suppressed by the metalloproteinase inhibitor, phosphoramidon, in contrast to th e case with intact preparations. When synthetic endothelin-1 was perfu sed in the endothelium-denuded mesentery, the peptide disappeared from the perfusate more rapidly than with intact preparations, suggesting that endothelin-1 generated from big endothelin-1 is effectively trapp ed by vascular smooth muscle cells in the endothelium-denuded preparat ion. Our results suggest that the endothelium is not essential for the conversion of big endothelin-1 to endothelin-1, in rat mesenteric art ery.