Oxyradicals as a mechanism of angiotensin-induced hypertension

Abstract

Angiotensin II (ANG II) generates reactive oxygen species (ROS) via an NADPH-oxidase in vascular system and leukocytes. ROS increase the formation of isoprostanes, which in turn increase the synthesis and release of endothelin (ET). ROS, isoprostane and ET are vasoconstrictors. ROS degrade nitric oxide (NO) a vasodilator. Superoxide, a member of the ROS family reacts with NO to generate peroxynitrite a potent oxidant. Peroxynitrite stimulates PGH₂ synthase and hence increases the production of thromboxane A₂, a vasoconstrictor. Peroxynitrite also inhibits prostacyclin synthase that would result in decreased synthesis of prostacyclin a vasodilator. ROS and peroxynitrite would produce endothelial cell dysfunction resulting in a decrease in production of vasodilators and hence unopposed action of circulating vasoconstrictors. Ang II-induced hypertension is attenuated by antioxidants and this effect is associated with a reduction in oxidative stress. The evidence to date suggests that Ang II releases ROS by stimulating NADPH-oxidase in the vascular system and leukocytes. ROS directly or through synthesis and release of isoprostanes and ET, in activation of NO and generation of peroxyinitrite produces vasoconstriction and hence induce hypertension.