In vitro and in vivo studies of the derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide

V. V. Khramtsov, D. I. Utepbergenov, Ya Yu Vol'dman, L. P. Vlasenko, A. L. Markel', I. A. Kirilyuk, I. A. Grigor'ev, D. G. Mazhukin, A. Ya Tikhonov, L. B. Volodarskij

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The series of nitronylnitroxyl radicals (NNR) were studied as paramagnetic scavengers of nitric oxide. These radicals react with NO with rate constants of (0.6-1.1)·104 M-1·sec-1 forming stable iminonitroxyl radicals. They can be used to assay nitric oxide in solutions by EPR spectroscopy; the sensitivity of the method is 1 μM for the detection of NO concentration and 0.3 nM/sec for the measurements of the rates of NO generation for 1 h in 0.2 ml sample. To overcome fast reduction of the radicals in biological samples, charged NNR was incorporated into the inner volume of large unilamellar phosphatidylcholine liposomes thus decreasing the rates of NNR reduction about 1000-fold. The method was used for the NO synthase activity assay in rat cerebellum cytosol. NNR was used to study the kinetics of the decomposition of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD). Several DD derivatives at 5-80 μM concentrations are very effective vasodilators in perfused rat tail artery. Intraperitoneal injection of several DD (40-200 μg/kg weight) in hereditary hypertensive rats (ISIAH-strain) significantly (by 30%) decreased systolic arterial blood pressure whereas similar effect of trinitroglycerol was detected at significantly higher dose (900 μg/kg weight).

Original languageEnglish
Pages (from-to)1731-1742
Number of pages12
JournalBiokhimiya
Volume61
Issue number7
Publication statusPublished - Jul 1996
Externally publishedYes

Fingerprint

Rats
Nitric Oxide
Derivatives
Assays
Blood pressure
Phosphatidylcholines
Vasodilator Agents
Liposomes
Nitric Oxide Synthase
Paramagnetic resonance
Rate constants
Spectroscopy
Decomposition
Kinetics

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Khramtsov, V. V., Utepbergenov, D. I., Vol'dman, Y. Y., Vlasenko, L. P., Markel', A. L., Kirilyuk, I. A., ... Volodarskij, L. B. (1996). In vitro and in vivo studies of the derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide. Biokhimiya, 61(7), 1731-1742.

In vitro and in vivo studies of the derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide. / Khramtsov, V. V.; Utepbergenov, D. I.; Vol'dman, Ya Yu; Vlasenko, L. P.; Markel', A. L.; Kirilyuk, I. A.; Grigor'ev, I. A.; Mazhukin, D. G.; Tikhonov, A. Ya; Volodarskij, L. B.

In: Biokhimiya, Vol. 61, No. 7, 07.1996, p. 1731-1742.

Research output: Contribution to journalArticle

Khramtsov, VV, Utepbergenov, DI, Vol'dman, YY, Vlasenko, LP, Markel', AL, Kirilyuk, IA, Grigor'ev, IA, Mazhukin, DG, Tikhonov, AY & Volodarskij, LB 1996, 'In vitro and in vivo studies of the derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide', Biokhimiya, vol. 61, no. 7, pp. 1731-1742.
Khramtsov, V. V. ; Utepbergenov, D. I. ; Vol'dman, Ya Yu ; Vlasenko, L. P. ; Markel', A. L. ; Kirilyuk, I. A. ; Grigor'ev, I. A. ; Mazhukin, D. G. ; Tikhonov, A. Ya ; Volodarskij, L. B. / In vitro and in vivo studies of the derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide. In: Biokhimiya. 1996 ; Vol. 61, No. 7. pp. 1731-1742.
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abstract = "The series of nitronylnitroxyl radicals (NNR) were studied as paramagnetic scavengers of nitric oxide. These radicals react with NO with rate constants of (0.6-1.1)·104 M-1·sec-1 forming stable iminonitroxyl radicals. They can be used to assay nitric oxide in solutions by EPR spectroscopy; the sensitivity of the method is 1 μM for the detection of NO concentration and 0.3 nM/sec for the measurements of the rates of NO generation for 1 h in 0.2 ml sample. To overcome fast reduction of the radicals in biological samples, charged NNR was incorporated into the inner volume of large unilamellar phosphatidylcholine liposomes thus decreasing the rates of NNR reduction about 1000-fold. The method was used for the NO synthase activity assay in rat cerebellum cytosol. NNR was used to study the kinetics of the decomposition of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD). Several DD derivatives at 5-80 μM concentrations are very effective vasodilators in perfused rat tail artery. Intraperitoneal injection of several DD (40-200 μg/kg weight) in hereditary hypertensive rats (ISIAH-strain) significantly (by 30{\%}) decreased systolic arterial blood pressure whereas similar effect of trinitroglycerol was detected at significantly higher dose (900 μg/kg weight).",
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AU - Khramtsov, V. V.

AU - Utepbergenov, D. I.

AU - Vol'dman, Ya Yu

AU - Vlasenko, L. P.

AU - Markel', A. L.

AU - Kirilyuk, I. A.

AU - Grigor'ev, I. A.

AU - Mazhukin, D. G.

AU - Tikhonov, A. Ya

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