In vitro and in vivo studies of derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide Full article
| Journal |
Biochemistry (Moscow)
ISSN: 0006-2979 |
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| Output data | Year: 1996, Volume: 61, Number: 10, Pages: 1223-1231 Pages count : 9 | ||||||||
| Tags | Arterial pressure; Nitric oxide; Nitronylnitroxyl radical; NO donor; NO scavenger; Vasodilator | ||||||||
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Abstract:
Various nitronylnitroxyl radicals (NNR) were studied as paramagnetic scavengers of nitric oxide. The radicals react with NO with rate constants of (0.6-1.1)·104M-1·sec-1, forming stable iminonitroxyl radicals. This can be used to measure nitric oxide in solutions by EPR spectroscopy, the sensitivity being 1 μM for detection of NO and 0.3 nM/sec for measuring the NO generation rate in 1 h in a 0.2-ml sample. To overcome fast reduction of the radicals in biological samples, an NNR with a charged functional group was incorporated into the inner volume of large unilamellar phosphatidylcholine liposomes, decreasing the rates of NNR reduction by about 1000-fold. The approach was used to measure the activity of NO synthase from rat cerebellum. NNR were used to study the decomposition of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD), supporting a previously proposed mechanism for DD decomposition with liberation of two mo- lecules of nitric oxide per DD molecule. The rate constants for DD decomposition are in the range from 10-8 to 6.5·10-7 sec-1 in water and from 3·10-7 to 1.6·10-5 sec-1 in dimethylsulfoxide at 37°C. Experiments with perfused rat tail artery showed that some DD derivatives are highly effective vasodilators at concentrations from 5 to 80 μM. Significant (up to 30%) decrease in systolic arterial blood pressure was observed in genetically hypertensive rats (ISIAH-strain) when some DD were injected intraperitoneally (40-200 μg/kg body weight), while the same effect of trinitroglycerin (TNG) was found at much higher dose (900 μg/kg).
Cite:
Khramtsov V.V.
, Utepbergenov D.I.
, Woldman Y.Y.
, Vlassenko L.P.
, Markel A.L.
, Kiriljuk I.A.
, Grigor'ev I.A.
, Mazhokin D.G.
, Tikhonov A.Y.
, Volodarsky L.B.
In vitro and in vivo studies of derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide
Biochemistry (Moscow). 1996. V.61. N10. P.1223-1231. WOS Scopus РИНЦ
In vitro and in vivo studies of derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide
Biochemistry (Moscow). 1996. V.61. N10. P.1223-1231. WOS Scopus РИНЦ
Identifiers:
| Web of science: | WOS:A1996VX61400001 |
| Scopus: | 2-s2.0-4243084536 |
| Elibrary: | 13246587 |