Alternatively or additionally, cholestasis may have caused a pre-existent vasoconstrictive state that rendered the hepatic microcirculation unreceptive to ATV-mediated inhibition of vasoconstrictors (endothelin-1, thromboxane A2) and upregulation of NO, which would generally result in improved microcirculation, oxygen delivery, and energy metabolism. Here, EDN1 is linked to cholestasis.