peroxynitrite

In vessels, the main ROS sources are xanthine oxidase, mitochondria, cyclooxygenases, NADPH oxidase and uncoupled nitric oxide (NO) synthase (NOS).

The ROS superoxide (O2-) reacts with NO to produce peroxynitrite, eliminating the NO that was available for vasodilation.

Peroxynitrite and ROS oxidize the NOS cofactor tetrahydrobiopterin (BH4), which results in NOS uncoupling and ongoing production of ROS.

Peroxynitrite and ROS induce DNA strand breaks that result in activation of the DNA repair enzyme poly-ADP-ribose polymerase (PARP).

Activated PARP consumes large amounts of energy, depleting energy-rich substrates and compromising endothelial function.

In addition, peroxynitrite inhibits the synthesis of the vasodilator prostacyclin (PGI2) and further impairs the ability of vessels to dilate.