S-glutathionylation uncouples eNOS and regulates its cellular and vascular function

The enzyme eNOS (endothelial nitric oxide synthase) is vital for regulating vascular function as it can produce both the vasodilator nitric oxide and the vasoconstrictor superoxide. Jay Zweier and colleagues show that a modification associated with oxidant stress, S-glutathionylation, switches the enzyme from forming nitric oxide to forming superoxide. In hypertensive vessels, S-glutathionylation of eNOS is increased, and this is associated with impaired endothelium-dependent vasodilation. Oxidant stress occurs in many diseases including heart attack, stroke, diabetes and cancer. This work suggests that agents that reset this redox switch, thereby restoring normal nitric oxide synthase function, may have therapeutic potential.