Nitric Oxide and Peroxynitrite

Nitric oxide is a potent pulmonary vasodilator that can be delivered via inhalation (Pepke-Zaba et al. 1991, PisoN et al. 1993, Rimar and Gillis 1995, Day et al. 1996, Nelin and Hoffman 1998). In the neonatal pig, inhaled nitric oxide dilated the smaller arteries more than the larger ones (Guar i n et al. 2001). 

Phenotypic heterogeneity among endothelial cell populations may account for important organ- 

Lipopolysaccharide (0.5 /tg/ml) and tumour necrosis factor-a (0.5 ng/ml) treatment increased l-arginine metabolism to both NO and urea in bovine pulmonary arterial endothelial cell cultures and resulted in increased levels of cationic amino acid transporter-2 mRNA (Nelin et al. 2001). 

To determine the potential role of nitric oxide in the vascular remodelhng induced by hypoxia, Quinlan et al. (2000) exposed wild-type [WT(+/+)] and endothehal NOS-deficient [(-/-)] mice to normoxia or hypoxia (10 % O2) for 2,4, and 6 days or for 3 weeks. Smooth muscle a-actin and von Willebrand factor immimohistochemistry revealed significantly less muscularization of small vessels in hypoxic eNOS(-/-) mouse lungs than in WT(+/+) mouse lungs at early time points, a finding that correlated with decreases in prohferating vascular cells (5-bromo-2 -deoxyuridine positive) at 4 and 6 days of hypoxia in the eNOS(-/-) mice. After 3 weeks of hypoxia, both mouse types exhib- 

3-Morpholinosydnonimine (SlN-1), which generates ONOO- by releasing O2 - and NO essentially in a simultaneous manner, significantly inhibited Ca signalling (Elliott 1996). Initially, the inhibitory effect of 1 mM SIN-1 was selective toward agonist-stimulated influx of external Ca. At later time points, SIN-1 additionally depleted internal stores of releasable Ca.  

---

H. Yamasaki and Y. Sakihama, Simultaneous production of nitric oxide and peroxynitrite by plant nitrate reductase in vitro evidence for the NR-dependent formation of active nitrogen species. FEBS Lett. 468, 89-92 (2000). 

Examples of Biological Functions of Nitric Oxide and Peroxynitrite... 

The above examples of biological activities of nitric oxide and peroxynitrite are of course just a small part of publications in this field. Although both nitrogen compounds can act as... 

Nitric oxide and peroxynitrite contribute to oxidative damage 569 Production of eicosanoids from polyunsaturated fatty acids such as arachidonic acid may generate reactive oxygen species 570 Brain antioxidant defenses modify ischemia-reperfusion injury 570 Reactive oxygen species may modify both the excitotoxic and the apoptotic components of ischemic brain damage 570... 

Wizemann, T.M. et al., Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia, J. Leukoc. Biol., 56, 759, 1994. 

D. Washo-Stultz, N. Hoglen, H. Bernstein, C. Bernstein and C. M. Payne, Role of nitric oxide and peroxynitrite in bile salt-induced apoptosis relevance to colon carcinogenesis, Nutr. Cancer, 1999, 35(2), 180. 

Generation of peroxynitrite in the vascular compartment as the result of ischemia/reperfusion. The introduction of oxygen following ischemia will initiate the simultaneous production of superoxide and nitric oxide. Neutrophils and macrophages may also generate nitric oxide and peroxynitrite directly. The rate of forming peroxynitrite will increase as the pnxluct of nitric oxide and superoxide concentration, and thus will increase rapidly under conditions when both are produced simultaneously. 

The redox potentials of various oxidants derived from nitric oxide and peroxynitrite are summarized in Table 4. Clearly, as the adducts of molecular oxygen and nitric oxide become more reduced, they form substantially stronger oxidizing agents. In effect, addition of one electron makes these nitrogen oxides more ready to accept the next. The precise pathway of decomposition followed is influenced by what types of target molecules come in contact with peroxynitrite and is... 

Van der Veen R. C. and Roberts L. J. (1999). Contrasting roles for nitric oxide and peroxynitrite in the peroxidation of myelin lipids. J. Neuroimmunol. 95 1-7. 

Ginko biloba reduces the formation of nitric oxide and peroxynitrite Metallothionein... 

Chang, T., Wang, R., and Wu, L. 2005. Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells. Free Radio Biol Med 38 286-293. 

W4. Wang, P., and Zweier, J. L., Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury. J. Biol. Chem. 271,29223-29230 (1996). 

Castro, L.A., Robalinho, R.L., Cayota, A., Meneghini, R., Radi, R. (1998). Nitric oxide and peroxynitrite-dependent aconitase inactivation and iron-regulatory protein-1 activation in mammalian fibroblasts. Arch. Biochem. Biophys. 359 215-24. 

Brunelli, L., Crow, J.P., Beckman, J.S. (1995). The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Arch. Biochem. Biophys. 316 327-34. 

Narayan, M., Wright, V.P., Berliner, L.J. et al. (1997). Do nitric oxide and peroxynitrite contribute to hydroxylation reactions in fatigued diaphragm FASEB J. 11 A72. 

Lizasoain, I., Moro, M.A., Knowles, R.G., Darley-Usmar, V., Moncada, S. (1996). Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose. Biochem. J. 314 877-80. 

Beckman J, Tsai JH (1994) Reactions and diffusion of nitric oxide and peroxynitrite. The Biochemist 16 8-10. 

Burney, S., Caulfield, JL, Niles, JC, Wishnok, JS, and Tannenbaum, SR. 1999. The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 424 37-49. 

---