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).
| Original language | English |
|---|---|
| Pages (from-to) | 1223-1231 |
| Number of pages | 9 |
| Journal | Biochemistry (Moscow) |
| Volume | 61 |
| Issue number | 10 |
| Publication status | Published - 1996 |
| Externally published | Yes |
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Keywords
- Arterial pressure
- Nitric oxide
- Nitronylnitroxyl radical
- NO donor
- NO scavenger
- Vasodilator
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
Cite this
In vitro and in vivo studies of derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide. / Khramtsov, V. V.; Utepbergenov, D. I.; Woldman, Ya Yu; Vlassenko, L. P.; Markel, A. L.; Kiriljuk, I. A.; Grigor'ev, I. A.; Mazhokin, D. G.; Tikhonov, A. Ya; Volodarsky, L. B.
In: Biochemistry (Moscow), Vol. 61, No. 10, 1996, p. 1223-1231.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vitro and in vivo studies of derivatives of 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide
AU - Khramtsov, V. V.
AU - Utepbergenov, D. I.
AU - Woldman, Ya Yu
AU - Vlassenko, L. P.
AU - Markel, A. L.
AU - Kiriljuk, I. A.
AU - Grigor'ev, I. A.
AU - Mazhokin, D. G.
AU - Tikhonov, A. Ya
AU - Volodarsky, L. B.
PY - 1996
Y1 - 1996
N2 - 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).
AB - 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).
KW - Arterial pressure
KW - Nitric oxide
KW - Nitronylnitroxyl radical
KW - NO donor
KW - NO scavenger
KW - Vasodilator
UR - http://www.scopus.com/inward/record.url?scp=4243084536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4243084536&partnerID=8YFLogxK
M3 - Article
VL - 61
SP - 1223
EP - 1231
JO - Biochemistry. Biokhimiia
T2 - Biochemistry. Biokhimiia
JF - Biochemistry. Biokhimiia
SN - 0006-2979
IS - 10
ER -