Functions and significance of nitric oxide in patho-physiological processes

Abstract

Nitric oxide (NO) is an important signaling molecule that regulates a diverse range of physiological processes in many tissues. NO is enzymatically synthesized from L-arginine by three isoforms of nitric oxide synthase (NOS). It plays an important role in a large number of normal physiological (regulation of blood pressure, neurotransmission, wound repair and host defense mechanisms) as well as in patho-physiological (inflammation, infection, apoptosis, neoplastic diseases, liver cirrhosis, diabetes) processes. With an unpaired electron, NO is a strong pro-oxidant produced in conditions like sepsis. It also exerts its effect through other free radicals such as superoxide and hydroxyl ions and causes oxidative stress within the cell. Reactive nitrogen intermediates play a central role in cell death (apoptosis), which is mediated by the induction of pro-inflammatory cytokines such as tumour necrosis factor. NO mediated apoptosis occurs in various cell types such as macrophages, lymphocytes, thymocytes, endothelial cells. At lower concentration (10 nM-1 μM) NO has been shown to have antiapoptotic effect, which is cyclic GMP dependent. One of the most beneficial functions of NO is its implication in host defense against intracellular pathogens (Salmonella and Leishmania). Its derivatives such as per-oxynitrite are strong bactericidal in nature. Involvement of NO in inflammatory responses has been shown not only in experimental models but also in human inflammatory diseases. The antioxidant and antiapoptotic properties make this molecule of great therapeutic significance.