Nitric oxide, synthesis

Nitric oxide is synthesized from the amino acid arginine in a reaction catalysed by NOS I-arginine + 02 + NADPH — citrulline + NADP+ + NO (thiol, tetrahydrobiopterin, FMN and FAD being requisite cofactors in this process). NO subsequently acts by activating soluble GC, thereby successively causing elevation of cGMP and PKG activation. NO can also act by activating Ca2 1 -dependent K+ channels. 

Nitric oxide and NOS can be constitutive or inducible. Constitutive nNOS and eNOS occur in neuronal and endothelial cells, respectively, and are activated by CaM. In endothelial cells acetylcholine, bradykinin or blood flow derived shear stress elevate cytosolic Ca2+ with the successive consequences of eNOS activation by CaM, NO production, GC activation by NO, elevation of cGMP, PKG activation, specific protein phosphorylation, vascular smooth muscle relaxation and vascular dilation. 

5 Nitric Oxide Synthesis The catalytic oxidation of nitrogen 

The glow discharge experiments were performed in a flow-circulation 

The relative increases in the steady state concentration of NO for different reaction mixtures given in Table 6 show that a stoichiometric mixture over Pt 

To explain the dependence of NO yield on composition a mechanism was proposed in which N ions play an important role. In the case of air the mechanism included reactions for the decomposition of NO  

With stoichiometric mixture there is an increase of the oxygen concentration in the mixtiure which prevents the decomposition of NO. This is evident from the analysis of the kinetic constants (Table 6) ki does not change on passing from air to a stoichiometric mixture, while k2 greatly diminishes, that is, the reaction 

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Pryor GT Persisting neurotoxic consequences of solvent abuse a developing animal modelfortoluene-inducedneurotoxicity. NlDAResMonogr 101 136—166,1990 Pudiak CM, Bozarth MA The effect of nitric oxide synthesis inhibition on intravenous cocaine self-administration. Prog Neuropsychopharmacol Biol Psychiatry 26 189— 196, 2002... 

Mouse peritoneal macrophages that have been activated to produce nitric oxide by 7-interferon and lipopolysac-charide were shown to oxidize LDL less readily than unactivated macrophages. Inhibition of nitric oxide synthesis in the same model was shown to enhance LDL oxidation (Jessup etal., 1992 Yates a al., 1992). It has recently been demonstrated that nitric oxide is able to inhibit lipid peroxidation directly within LDL (Ho etal., 1993c). Nitric oxide probably reacts with the propagating peroxyl radicals thus terminating the chain of lipid peroxidation. The rate constant for the reaction between nitric oxide and peroxyl radicals has recently been determined to be 1-3 X10 M" s (Padmaja and Huie, 1993). This... 

Farrell, A.J., Blake, D.R., Palmer, R.J. and Moncada, S. (1992). Increased concentrations of nitrite in synovial fluid and serum samples surest increased nitric oxide synthesis in rheumatic diseases. Ann. Rheum. Dis. 51, 1219-1222. 

Yamada, T., Sartor, R.B., Marshall, S. and Grisham, M.B. (1992). A chronic model of distal colitis induced by bacterial cell wall polymers activation of leukocyte nitric oxide synthesis. Gastroenterology 102, A715. 

B2. Balligand, J. L., Ungureanu, D Kelly, R. A., Kobzik, L., Pimental, D Michel, T and Smith, T. W., Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. J. Clin. Invest. 91, 2314-2319(1993). 

N5. Nava, E Palmer, M. J., and Moncada, S., Inhibition of nitric oxide synthesis in septic shock How much is beneficial . Lancet 338, 1555-1557 (1991). 

Lastra AL, Ramirez TO, Salazar L, Martinez M, Trujillo-Ferrara J. The ambrosanolide cumanin inhibits macrophage nitric oxide synthesis some structural considerations. J Ethnopharmacol 2004 95 221-227. 

Kapas, L., Fang, J. 8r Krueger, J. M. (1994a). Inhibition of nitric oxide synthesis inhibits rat sleep. Brain Res. 664, 189-96. 

A. Meulemans, A brain nitric oxide synthase study in the rat production of a nitroso-com pound NA and absence of nitric oxide synthesis. Neurosci. Lett. 321,115-119 (2002). 

S.R. Thom, D. Fisher, J. Zhang, V.M. Bhopale, S.T. Ohnishi, Y. Kotake, T. Ohnishi, and D.G. Buerk, Stimulation of perivascular nitric oxide synthesis by oxygen. Am. J. Physiol.-Heart Circul. Physiol. 284, HI230-1239 (2003). 

Reactive nitrogen species are another factor of free radical damage in rheumatoid arthritis, although their role is less studied than that of oxygen radicals. Stichtenoth and Frolich [242] pointed out that the inhibition of nitric oxide synthesis had beneficial effects in humans. Mazzetti et al. [243] found that IL-1(3 stimulated NO production in RA chondrocytes. We demonstrated that NO synthase of RA neutrophils generated the enhanced amount of peroxynitrite [234]. Nitric oxide and oxygen radicals are also important inducers of death of human osteoarthritic synoviocytes [244]. 

Green, S.J. and Nacy, C.A., Antimicrobial and immunopathologic effect of cytokine-induced nitric oxide synthesis, Curr. Opin. Infect. Dis., 6, 384, 1993. 

Zweier, J. L., Samouilov, A., Kuppusamy, P., Non-enzymatic nitric oxide synthesis in biological systems. Biochim. Biophys. Acta 1411 (1999), p. 250-262... 

Archer, S. L., Hampl, V. N. G., Monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings trouble in paradise, Biochem. Biophys. Res. Commun. 188 (1992), p. 590-596... 

Nitric oxide Ginsenosides enhance nitric oxide synthesis, with effects in the endothelium of the lungs, heart, and kidneys and in the corpus cavernosum (Kim H et al. 1992 Ko et al. 1996). This is a potential mechanism of ginseng-associated vasodilation. Effects on neuronal nitric oxide have not been specifically investigated. 

Vascuiar and sexuai effects Ginseng saponin has demonstrated vasoactive effects. It activates the release of NO from bovine aortic endothelium, and from the endothelial cells and perivascular nerve of the rabbit corpus cavernosum (Kim HS et al. 1998 Ko et al. 1996 Choi and Seong 1995 Chen and Lee 1995). Nitric oxide synthesis is also observed in the endothelium of the lung, heart, and kidney (Gillis 1997). 

Mozaffarian N, Berman JW, Casadevall A. Enhancement of nitric oxide synthesis by macrophages represents an additional mechanism of action for amphotericin B. Antimicrob Agents Chemother 1997 41 1825. 

Malin DH, Lake JR, Shenoi M, Upchurch TP, Johnson SC, Schweinle WE, Cadle CD (1998b) The nitric oxide synthesis inhibitor nitro-L-arginine (L-NNA) attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 140 371-377... 

Changes in the concentration of arginine, via arginase activity, can play a role in regulating the rate of nitric oxide synthesis. Nitric oxide is a messenger molecule that has several roles. One is to increase the activity of the enzyme guanyl cyclase, which increases the concentration of cyclic GMP. The latter causes vasolidation in peripheral... 

Komori K, Tsujimura A, Takao T, Matsuoka Y, Miyagawa Y, Takada S, Nonomura N, Okuyama A. (2008) Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3, 5-monophosphate (cGMP) pathway in human corpus cavemosal smooth muscle cells. J Sex Med 5 1623-1635. 

Vale A, Green S, Montgomery AM, Shall S (1998) The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J Psychopharmacol 12 268-272 Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41 -residue ovine hypothalamic peptide that stimulates secretion of corticotropin and p-endorphin. Science 213 1394-1397... 

Liu, D., Homan, L.L., and Dillon, J.S., Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5 -monophosphate-dependent mechanism. Endocrinology, 145, 5532, 2004. 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Macrophages were simutated with phorbol 1 Z-myristate 13-acetate, and nitric oxide synthesis was inhibited with N-methyl-L-arginine. Percent NO, represents the percentage of NO, compared... 

Hibbs, J. B., Jr., Westenfelder, C., Taintor, R., Vavrin, Z., Kablitx, C., Baranowski, R. L., Ward, J. H., Menlove, R. L., McMurry, M. P., Kushner, J. P., and Samlowski, W. E. (1992). Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J. Clin. Invest. 89, 867-877. 

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