Endothelin stimulates degradation of phospholipids in isolated rat hearts

The abilities of endothelin-1 to cause cellular injury and to enhance the levels of inositol-1,4,5-triphosphate and the breakdown of [14C]arachidonate-labeled phospholipids have been examined in the isolated rat heart model. In 10 minutes, endothelin at 1 and 3 nM concentrations significantly increased the myocardial release of creatine kinase, suggesting endothelin-induced cell injury. The enhanced levels of myocardial inositol-1,4,5-triphosphate and diacyl glycerol by endothelin also suggest the increased breakdown of phosphatidylinositol-4,5-bisphosphate. In addition, endothelin also increased the degradation of other membrane phospholipids as observed by (1) a decrease in [14C]arachidonate radiolabel in phospholipids, (2) an increase in [14C]radiolabel in non-esterified fatty acids and triacyl glycerol, and (3) increased levels of non-esterified fatty acids. The potential role of endothelin-1 in myocardial ischemia-reperfusion injury is discussed.