First, endothelin-A receptor–dependent vasoconstriction may contribute to progressive renal injury, which has a strong hemodynamic component.44 Second, ET-1, via endothelin-B receptors, can drive epithelial-mesenchymal transition and promote renal fibrosis.45Gpr81−/− mice did not respond to ischemia-reperfusion with an increase in TNF-α or collagen 1a1 production, and the disconnection between extracellular lactate and ET-1 may account for this. The gene discussed is EDN1; the disease is renal fibrosis.