Not only has the present study certified that ERα, ERβ and GPER induce EDH-mediated vasorelaxation via PLC/IP3/IP3R pathway, but in sepsis when ACh-induced vasorelaxation was impaired, E2 pretreatment could rescue it to increase blood flow to the septic organs via nongenomic action-mediated PLC/IP3/IP3R pathway to finally exert beneficial effects (Figure 9C). The gene discussed is ITPR1; the disease is Sepsis.