Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase

Feelisch, Martin; Noack, E.

doi:10.1016/0014-2999(87)90493-6

Cited by 868 publications

(419 citation statements)

References 18 publications

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“…A standard of a-tocopheryl quinone was produced by incubation of a-tocopherol with FeCi, and subsequent chromatographic purificatton. globin method [17,18]. The formation of thiobarbituric acid-reactive substances was measured according to [16].…”

Section: Incubationsmentioning

confidence: 99%

Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

1993

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SIN‐1 which spontaneously decomposes to yield nitric oxide (NO. and Superoxide anion (O2 .− radicals caused a loss of microsomal α‐tocopherol paralleled by the formation of α‐tocopheryl quinone. The loss was partially prevented by Superoxide dismutase but not by catalase. The SIN‐1‐induced loss of α‐tocopherol also occurred when tocopherol was dissolved in ethanol/potassium phosphate buffer (20/80, v/v). Likewise, addition of authentic NO. to α‐tocopherol dissolved in ethanol resulted in loss of the vitamin and quinone formation. These results suggest that NO. or its products such as peroxynitrite or nitrogen dioxide react with α‐tocopherol, the quinone derivative being a major oxidation product. Depletion of vitamin E by NO. may contribute to tissue injury, e.g. in neuronal tissues.

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Section: Incubationsmentioning

confidence: 99%

Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

1993

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“…Moreover, the addition of D-glucose, or L-glucose to PN in the superfusate, suggests that PN can react with organic molecules, including sugars and bicarbonate, to form an NO donor [5,41,58,61,63]. However when electrochemically assayed, the reaction between PN and glucose to generate NO required both Cu ++ and L-cysteine, a requirement similar to that found for other organic nitrates, such as nitroglycerin (GTN), or to nitrites such as amyl nitrite [64][65][66]. Additionally, PN reacted with L-glucose as well as to other molecules with functional alcohol groups such as fructose, glycerol, or glyceraldehyde [61].…”

Section: Vasorelaxant Properties Of Peroxyni-tritementioning

confidence: 85%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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“…The first-order generation of nitrite was observed for these drugs, the rate constants being 0.0411 ±0. (7,8) have been reported to release NO spontaneously in solution. Actually, FK409 and SIN-1 spontaneously generated nitrite, an oxidative product of NO, with rates in the rank order of SIN-1 > FK409 in PB solution.…”

Section: Nitrite Generation In Rat Plasmamentioning

confidence: 99%

“…1) and sodium nitroprusside (SNP, Fig. 1) have been also reported as NO releasers that liberate NO spontaneously (7,8). In addition, these compounds have been also suggested to show vasorelaxant and antiplatelet effects (9,10).…”

mentioning

confidence: 99%

Close Correlation between Nitric Oxide (NO) Formation from NO Releasers and the Biological Activities of These Agents in Rats

Kita¹,

Fukuyama

Hirasawa³

1995

Japanese Journal of Pharmacology

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ABSTRACT-The aim of this study was to clarify the difference in the profiles of nitric oxide (NO) formation of three NO releasers and to examine the correlation between NO formation from these drugs and their biological activities in rats. (±)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and 3-morpholinosydnonimine (SIN-1) spontaneously generated nitrite, an oxidative product of NO, in sodium phosphate buffer (PB) solution. On the other hand, sodium nitroprusside (SNP) did not generate nitrite. The rank order of the concentrations of nitrite generated was SIN-1 >FK409>SNP.In biological studies using rats, these drugs showed anti-platelet effects and in vitro vasorelaxant and hypotensive effects with potencies in the rank order of FK409 > SIN-1 > SNP and SNP > FK409 > SIN-1, respectively. These drugs generated nitrite with concentrations in the rank order of FK409 > SIN-1 > SNP and SNP > FK409 > SIN-1 in rat plasma and in PB solution with L-cysteine (Cys), respectively. In conclusion, three NO releasers liberate NO with NO-releasing rates of different rank orders under different incubation conditions, and the anti-platelet effects and vasorelaxant and hypotensive effects of these NO releasers closely correlate with NO formation from the compounds in the plasma and PB solution with Cys, respectively, but not with that in PB solution without Cys.Keywords: FK409, 3-Morpholinosydnonimine (SIN-1), Sodium nitroprusside (SNP), Nitric oxide (NO) Fig. 1) is a structurally unique vasodilator discovered from the fermentation products of Streptomyces griseosporeus (1). FK409 has produced a potent vasorelaxation mediated by the elevation of cyclic GMP in isolated dog coronary artery (2), rabbit aorta (3) and rat aorta (4). In addition, FK409 has shown a potent inhibition of platelet aggregation in human (5) and rat (6) platelet-rich plasma. Recently, we have reported that these biological actions of FK409 can be accounted for by spontaneous nitric oxide (NO) release following decomposition of the compound (5). However, the NO-releasing pathway of FK409 remains unclear.3-Morpholinosydnonimine (SIN-1, Fig. 1) and sodium nitroprusside (SNP, Fig. 1) have been also reported as NO releasers that liberate NO spontaneously (7,8). In addition, these compounds have been also suggested to show vasorelaxant and antiplatelet effects (9, 10). Three NO releasers including FK409 have different structures, so it is considered that the profiles of NO formation of the compounds are different. It has not been reported whether NO formation from different types of spontaneous NO releaser correlates with the activities of the compounds in several biological studies.The purpose of this study was to clarify the difference in the profiles of NO formation of these NO releasers under several incubation conditions by measuring the concentration of nitrite, an oxidative product of NO, and examine the correlation between NO formation from these drugs and their biological activities. In biological studies, we evaluated in vitro anti-platelet ...

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Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase

Cited by 868 publications

References 18 publications

Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

Potential Benefits of Peroxynitrite

Close Correlation between Nitric Oxide (NO) Formation from NO Releasers and the Biological Activities of These Agents in Rats

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