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

Identifiers:

Web of science	WOS:A1996VX61400001
Scopus	2-s2.0-4243084536
Elibrary	13246587