One of the most well established defects in SEC-HSC crosstalk in liver injury is the decreased bioavailability of the vasodilator NO. which occurs independent of changes in eNOS expression and through defects in post-translational regulation of the enzyme within endothelial cells. During the process of liver injury, reduction of NO bioavailability occurs due to decreased synthesis of NO, enhanced inactivation of NO by the overproduction of superoxide (O2−) or both. An inactivation of eNOS occurs through an increase in cav-1 expression as well as one recently recognized protein, the G-protein-coupled receptor kinase 2 (GRK2), which directly interacts with and inhibits Akt, thereby decreasing eNOS activity.