Fluoroaluminate induces rapid release of endothelin-1 in the isolated perfused arterial and venous vessels of the rat mesentery.

1. Endothelin-1 (ET-1) production from endothelial cells is generally believed to be a process that happens over the course of hours. 2. When fluoroaluminate (AIF-4) was infused in the isolated perfused arterial and venous vessels of the rat mesentery there was an increase in perfusion pressure on both sides. 3. Treatment of mesentery with the endothelin receptor antagonists FR 139317 (ETA receptor selective) or PD 145065 (ETA-ETB receptor nonselective) caused inhibition on both the arterial and venous sides, suggesting that response is mediated predominantly by endothelin-1 through ETA receptors. 4. Endothelial denudation attenuated changes in perfusion pressure of mesenteric circulation generated by fluoroaluminate, but not those caused by exogenously added PGF2 alpha. 5. Our data demonstrate that there is an immediate release of endothelin-1 following fluoroaluminate infusion which could be partially mediated by activation of phospholipase C.