Nitric Oxide/Peroxynitrite Imbalance in Dysfunctional Endothelium–Clinical Implications

A dysfunctional endothelium is a common denominator of several cardiovascular diseases, including: hypertension, atherosclerosis, heart failure, diabetes, obesity and aging. Normal functioning endothelium mainly produces cytoprotective vasorelaxant, nitric oxide (NO) and traces of the cytotoxic vasoconstrictor, peroxynitrite (ONOO-). However, in dysfunctional endothelium, these proportions are reversed. The recent development of nanomedical systems allows for the simultaneous measurements, in situ, of small biomolecules like NO, ONOO- and superoxide (O2- in single a cell. NO is produced from L-arginine and O2 by a dimeric form of endothelial nitric oxide synthase (eNOS). However, destabilized/uncoupled eNOS dimer in dysfunctional endothelium can concomitantly produce O2- and NO. NO is a rapid scavenger of O2- to generate ONOO-, one of the most powerful oxidants in the cardiovascular system. ONOO- can also trigger a cascade of events leading to nitrosylation, nitration, apoptosis, necrosis,lipid peroxidation, enzyme inactivation and DNA modification.