Oxidative stress-mediated effects of angiotensin II in the cardiovascular system

Abstract

Angiotensin II (Ang II), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang II is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species (ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang II-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang II in the cardiovascular system. In particular, the involvement of Ang II-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca²⁺/calmodulin-dependent protein kinase II is an important molecule linking Ang II, ROS and cardiovascular pathological conditions.

Keywords: Angiotensin II; Arrhythmias; Hypertension; Hypertrophy; Ischemia-reperfusion; Mitochondria; Oxidative stress.

Figure 1. A schematic diagram illustrating the involvement of ROS signaling pathways in numeral Ang II-induced cardiovascular diseases

See main text for details. Ang II: Angiotensin II; AT₁R: Angiotensin II type 1 receptor; AT₂R: Angiotensin II type 2 receptor; ROS: Reactive Oxygen Species; CaMKII: calcium/calmodulin-dependent protein kinase II; I_Na: Sodium current; I_Ca,L: L-type calcium current; NCX: Sodium-Calcium current; SR: Sarcoplasmic reticulum; RyR: Ryanodine receptor; SERCA: SR Ca²⁺ ATPase; EAD: Early afterdepolarization; DAD: Delayed afterdepolarization.