Effect of Metformin on Oxidative Stress and Vascular Dysfunction Induced by Nitroglycerin Treatment in Rats

Abstract

Cardiovascular diseases (CVDs) are one of the leading causes of death in the world (Parlakpinar et al., 2013). Organic nitrates, particularly NG, has long been one of the key therapies for CVDs including coronary artery disease, acute myocardial infarction and congestive heart failure (Munzel et al., 2013). The ability of mammalian cells to convert NG to vaso-relaxant NO played a significant part in the discovery of the unique role of both NO and NG in acute angina and congestive heart disease (Fung, 2004). Despite of the clear benefits of NG treatment, yet it rapidly loses its hemodynamic and anti-ischemic clinical effectiveness when used as long-term therapy and this phenomenon is referred as nitrate tolerance (Parker, 2004). Moreover, acute high-dose of organic nitrates is likely to cause a similar loss of potency in the form of tachyphylaxis (Daiber and Munzel, 2015). This multifactorial phenomenon is likely related to impairment in NG biotransformation by inhibiting ALDH2 and generation of reactive oxygen species (ROS) as superoxide (O2.-) and reactive nitrogen species (RNS) as peroxynitrite (ONOO−) anions diminishing NO bioavailability (Gongadze et al., 2016). A cross talk between ROS, mitochondrial and endothelial dysfunction was documented in nitrate tolerance process. In this