Nitric oxide activity

Synthesized by soluble guanylyl cyclase and particulate guanylyl cyclase from guanosine triphosphate (GTP). Nitric oxide activates soluble guanylyl cyclase to enhance cyclic GMP production that contributes to various NO actions. Cyclic GMP is hydrolyzed by phosphodiesterases. Cyclic GMP binds to and activates cGMP-dependent protein kinase, phosphodiesterases, and Cyclic Nucleotide-regulated Cation Channels. 

Salvemini, D., Misko, T.P., Masferrer, J.L., Seibert, K., Citrrie, M.G. and Needleman, P. (1993). Nitric oxide activates cyclooxygenase enzymes. Proc. Natl Acad. Sci. USA 90, 7240-7244. 

The major limitation of nitrate therapy is the development of tolerance with continuous use. The loss of anti-anginal effects may occur within the first 24 hours of continuous nitrate therapy. While the cause of tolerance is unclear, several mechanisms have been proposed. These include depletion of the sulfhydryl groups necessary for the conversion of nitrates to nitric oxide, activation of neurohormonal systems, increased intravascular volume, and generation of free radicals that degrade nitric oxide. The most effective method to avoid tolerance and maintain the anti-anginal efficacy of nitrates is to allow a daily nitrate-free interval of at least 8 to 12 hours. Nitrates do not provide protection from ischemia during the nitrate-free period. Therefore, the nitrate-free... 

Prasad A, Narayanan S, Waclawiw MA, Epstein N, Quyyumi AA. The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. J Am Coll Cardiol 2000 36 1579-1586. 

Vasodilation is attributable to nitric oxide (NO), which is produced either directly from the nitroester or liberated by decomposition of NO intermediates (Feelisch and Noack 1987). Either glutathione in cells of vascular tissue or sulfhydryl groups of proteins in these tissues may be responsible for converting nitrates to NO. Nitric oxide activates guanylyl cyclase, which increases intracellular levels of cyclic guanosine 3 5 -monophosphate and thereby produces vasodilation (Kelly and Smith 1996 Robertson and Robertson 1996). 

A high-level ab initio study of related reactions of alkyl nitrates (RO—NO2) at the G3 and B3LYP/6-311-I— -G(d,p) levels has revisited the reactions of alkyl peroxy radicals (ROO") with nitric oxide. Activation barriers for the isomerization of RO—ONO to RO—NO2 were found to be too high to account for the formation of alkyl nitrates... 

Dtapier, J. C., Hirling, H., Wietzerbin, J., Kaldy, P., and Kuhn, L. C. (1993). Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J. 12, 3643-3649. 

Arnold, W. P., Mittal, C. K., Katsuki, S., and Murad, F. (1977). Nitric oxide activates guanylate cyclase and increases guanosine 3 5 -cyclic monophosphate levels in various tissue preparations. Proc. Nad. Acad. Sci. Ll.S.A. 74, 3203-3207. 

FIGURE 14-4. Once formed, nitric oxide activates the enzyme guanylyl cyclase (GC) by binding to iron (heme) in the active site of this enzyme. When activated, GC makes a messenger, (cyclic guanylate monophosphate (cGMP), which relaxes smooth muscle and performs other physiological functions. In the penis, relaxation of vascular smooth muscle opens blood flow and causes an erection. 

Knock GA, Mahn K, Mann GE, Ward JP, Aaronson PI. 2006. Dietary soy modulates endothelium-dependent relaxation in aged male rats Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity. Free Radic Biol Med 41 731-739. 

Zhang J., Dawson V. L., Dawson T. M., and Snyder S. H. (1994). Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263 687-689. 

Broillet MC, Firestein S (1997) Beta subunits of the olfactory cyclic nucleotide-gated channel form a nitric oxide activated Ca2+ channel. Neuron 18 951-8 Bugnon O, Schaad NC, Schorderet M (1994) Nitric oxide modulates endogenous dopamine release in bovine retina. Neuroreport 5 401—4... 

Body iron level and iron depletion play an important role in the gender differences seen in death from cardiac disease. There is a better correlation with heart disease mortality in iron levels compared with levels of cholesterol (5). It was found that risk of coronary heart disease (6) and carotid atherosclerosis (7) is associated with increased iron stores. However, impaired endothelium-derived nitric oxide activity may be without overt atherosclerosis in patients with risk factors and may be associated with the presence of atherosclerosis (4). Thus, endothelial dysfunction related to iron activity not only may be an early marker for cardiovascular risk but also may contribute to the pathogenesis of atherosclerosis (2) by the stimulation of low-density lipoproteins (LDL) and membrane lipid peroxidation (I) and may be a key to the understanding of early mechanism in the development of atheroma (7,8). Nakayama et al. (9) showed the role of heme oxygenase induction in the modulation of macrophage activation in atherosclerosis. However, Howes et al. (10) concludes that at the moment, the available evidence on iron hypothesis remains circumstantial. Moreover, Kiechl et al. (7) showed that the adverse effect of iron is hypercholesterolemia, In patients... 

Hosier J. S., Buxton K. L. and Smith B. H. (2000) Impairment of olfactory discrimination by blockade of GABA and nitric oxide activity in the honey bee antennal lobes. Behav. Neurosci. 114 (3), 514—525. 

R. T. Hepatic and splanchnic nitric oxide activity in patients with cirrhosis. Gut 1999, 44 749-753... 

In 1980 Ignarro and colleagues [53] published a possible mechanism requiring the reduction of nitrates intracellularly by sulphydryl donors to form an S-nitrosothiol active intermediate that in turn directly, or by degrading to nitric oxide, activated guanylate cyclase. As discussed above, these and other experiments led to the description of the EDRF and NOS enzyme systems. 

Stroes ES, LuscherTF, de Groot FG, Koomans HA, RabelinkTJ. Cyclosporin A increases nitric oxide activity n vivo. Hypertension 1997 29 570-575. 

Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. Hyperten. 1997 29(1 Pt2) 274-9. 

Mayoral P, Criado M, Hidalgo F, Flores O, Arvelo MA, et al. 1990. Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation. Clin. Sci. 96 297-305... 

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