Reactive Oxygen Species as Mediators of Calcium Signaling by Angiotensin II: Implications in Vascular Physiology and Pathophysiology.

摘要

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, and reactive nitrogen species, such as nitric oxide and peroxynitrite, are biologically relevant O(2) derivatives increasingly being recognized as important in vascular biology through their oxidation/reduction (redox) potential. All vascular cell types produce ROS primarily via membrane-associated NAD(P)H oxidase. ROS influence vascular function by modulating contraction/dilation, cell growth, apoptosis/anoikis, migration, inflammation, and fibrosis. An imbalance in redox state where prooxidants overwhelm antioxidant capacity results in oxidative stress. Oxidative excess and associated oxidative damage are mediators of altered vascular tone and structural remodeling in many cardiovascular diseases. ROS elicit these effects by influencing intracellular signaling events. In addition to modulating protein tyrosine kinases, protein phosphatases, mitogen-activated protein kinases, and transcription factors, ROS are important regulators of intracellular Ca(2+) homeostasis and RhoA/Rho kinase signaling. ROS increase vascular [Ca(2+)]i by stimulating inositol trisphosphate-mediated Ca(2+) mobilization, by increasing cytosolic Ca(2+) accumulation through sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase inhibition, and by stimulating Ca(2+) influx through Ca(2+) channels. Increased ROS generation enhances Ca(2+) signaling and up-regulates RhoA/Rho kinase, thereby altering vascular contractility and tone. The present review discusses the importance of ROS in angiotensin II signaling in vascular biology and focuses specifically on the role of oxidative stress in Ca(2+) signaling in the vasculature. Antioxid. Redox Signal. 7, 1302-1314.