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- BH4, tetrahydrobiopterin
- eNOS, endothelial nitric oxide synthase
- FAD, flavin adenine dinucleotide
- FMN, flavin mononucleotide
- NADPH, nicotinamide adenine dinucleotide phosphate
- NO, nitric oxide
Endothelium derived nitric oxide (NO) plays a major role in cardiovascular homeostasis. It has important anti-atherosclerotic properties which include regulation of vasomotor tone and vessel wall permeability, suppression of leucocyte adhesion to the endothelial surface, inhibition of platelet aggregation, and inhibition of vascular smooth muscle cell migration and proliferation. The important role of NO in the cardiovascular system is highlighted by key observations in animal models. Inhibition of endothelial NO synthase (eNOS), the enzyme that catalyses endothelial NO synthesis, accelerates atherogenesis. Similarly, genetic deletion of eNOS in mice leads to hypertension, defective vascular remodelling, vascular thrombosis, and enhanced leucocyte–endothelial cell interactions. In humans, all major cardiovascular risk factors, including hypercholesterolaemia, hypertension, diabetes, and smoking, have been associated with endothelial dysfunction, characterised by impaired NO bioavailability. Importantly, the impairment of NO mediated endothelial function is an independent predictor of adverse cardiac events.1 Taken together, current data strongly suggest that impaired NO activity is a crucial factor in the pathogenesis of cardiovascular disease. Improving endothelial NO bioavailability in vivo may reduce cardiovascular risk and has emerged as a major therapeutic goal.
SYNTHESIS AND DEGRADATION OF NITRIC OXIDE
In vivo NO bioactivity is determined by the balance between synthesis and degradation of NO. The biosynthesis of endothelial NO is catalysed by the enzyme eNOS and requires the amino acid L-arginine, nicotinamide adenine dinucleotide phosphate (NADPH), and molecular oxygen as substrates, as well as several cofactors and prosthetic groups. Inactivation of NO may occur by its reaction with oxyhaemoglobin in erythrocytes but also by reacting with superoxide anions, resulting in the formation of peroxynitrite. …