Nitrites nitric oxide released from

Nitric oxide release from blood vessels was first detected by chemiluminescence (Palmer et ai, 1987). In the original adaptations of the nitric oxide detector, perfusates from isolated vessels were directly mixed in a reflux chamber containing acetic acid and iodine. The iodine in the reflux chamber served to reduce any nitrites or nitroso-containing groups to nitric oxide, which was stripped from the chamber by a continuous stream of nitrogen or helium that flowed to the chemiluminescent detector. Replacement of the acetic acid with the less volatile trichloroacetic acid reduces problems with contamination of the nitric oxide detector (Dr. D. Harrison, Emory University, Atlanta, Georgia, personal communication, 1991). While extremely sensitive, the use of the acid reflux chamber also reduces the specificity of the assay, raising questions as to whether nitric oxide or a nitrosothiol is EDRF (Myers et ai, 1990). 

FIGURE 5 Effects of interleukin-4 (IL-4), IL-6, IL-8, and IL-10 on nitric oxide production from J774.2 cells in vitro. Cytokines (1 /ug/ml) were added to 96-well plates containing J774.2 cells 10 rain prior to the addition of lipopolysaccharide (LPS) (1 /rg/ml). Nitrite in the supernatant was assessed after 20 hr. Basal (Bas) release from unstimulated cells is also shown. Values are the means SE of quadruplicate measurements from five or six mice per group. , Significant (P < 0.05) inhibition of nitrite production by IL-4. 

In this metho d [ 124 ] nitrate, nitrate plus nitrite or nitrite alone are selectively reduced to nitric oxide, which is swept from the sample in a helium carrier gas flow. Nitric oxide is allowed to react with ozone in a nitrogen oxide analyser, where it forms nitrogen dioxide. The return of the nitrogen dioxide to the ground state is accompanied by release of a photon, which is detected by a photomultiplier. The integrated output of the photomultiplier over the time that the nitric oxide is pinged from the sample is proportional to the nitrite content of the sample. 

Fig. 9.5. The reaction of organic nitrites with thiols (Reaction a), and a general mechanism for the release of nitric oxide from S-nitroso thiols (Reactions b and c) [31]...

In summary, there is still much to understand about the nitrite reduction reaction. The crystal structures have shown how nitrite can bind to the di heme iron and protons can be provided to one of its oxygen atoms from two histidine residues. However, as yet no rapid reaction study has detected the release of product nitric oxide rather than the formation of the inhibitory dead-end ferrous di heme-NO complex. It is also not clear why the rate of interheme electron transfer is so slow over 11 A when nitrite or nitric oxide is the ligand to the d heme. 

Fig. 1. The EDRF/NO pathway in vascular smooth muscle. Vasodilatation by nitrates at a cellular level. Nitrates, nitrites, and nitroprusside-Na are able to release nitric oxide (NO), which stimulates the conversion of GTP into cyclic guanosine monophosphate (cGMP), thus causing vasodilatation. The release of EDRF (=NO) from endothelial cells can be stimulated by various endogenous compounds. Endogenous EDRF (=NO) then causes vasodilatation, similar to the NO released by...

In the process, the iron is reduced to the ferrous form. Ferric cytochrome c is reduced by nitric oxide through a nitrosyl intermediate to produce ferrous cytochrome c and nitrite (Orii and Shimada, 1978). The nitrosyl cytochrome c absorbs at 560 nm, which is slightly higher than the 550-nm peak observed for reduced cytochrome c. Nitric oxide may be an interference in the assay of superoxide from cultured cells by the cytochrome c method. When nitric oxide reacts with cytochrome c, there is an initial decrease in absorbance at 550 nm as the nitrosyl complex is formed followed by a rise in absorbance as the complex decomposes to nitrite and reduced cytochrome c. This is a potential artifact in studies measuring the release of superoxide from cultured endothelial cells or other cells that make nitric oxide. 

The dichloromethane extract from Wilbrandia ebracteata (p.o.) significantly reduced the paw elevation time (1 mg/kg) and cell influx (10 mg/kg) in zymosan-induced arthritis in rats. The same extract inhibited COX-2 activity, as measured by PGE2 production, without affecting that of COX-1. Moreover, nitrite release was clearly and significantly reduced at a dose of 10 mg/kg (p.o.). The analysis of the pharmacological data, together with the HPLC analysis of the extracts, points to an anti-inflammatory effect based on an associated reduction in nitric oxide (NO) release and COX-2 inhibition by the cucurbitacins... 

B. Exogenous Nitric Oxide Donors Nitric oxide is released from several important dmgs, including nitroprusside (Chapter 11), nitrates, (Chapter 12), and nitrites. Release from nitro-prusside occurs spontaneously in the blood in the presence of oxygen, while release from nitrates and nitrites is enzymatic, intracellular, and requires the presence of thiol compounds such tis cysteine. Tolerance may develop to nitrates and nitrites if endogenous thiol compounds are depleted. 

In contrast, drugs that release endogenous nitric oxide and donors of the molecule were in use long before nitric oxide was discovered and continue to be very important in clinical medicine. The cardiovascular applications of nitroprusside (Chapter 11) and the nitrates and nitrites (Chapter 12) have been discussed. The treatments of preeclampsia and of pulmonary hypertension and acute respiratory distress syndrome are currently under clinical investigation. Early results from the pulmonary disease studies appear promising, and one preparation of nitric oxide gas (INOmax) has been approved for use in neonates with hypoxic respiratory failure. 

Nitroprusside and organic nitrites (eg, amyl nitrite) and nitrates (eg, isosorbide dinitrate) contain NO groups that can be released as nitric oxide. Arginine is the normal source of endogenous nitric oxide. Histamine stimulates the production of nitric oxide from arginine. The answer is (C). 

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