[Studies of in vitro and in vivo derived 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide]. / Issledovaniia in vitro i in vivo proizvodnykh 1,2-diazetina i nitronilnitroksida v kachestve donorov i aktseptorov oksida azota.

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).10(4) 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 microM 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 microM concentrations are very effective vasodilators in perfused rat tail artery. Intraperitoneal injection of several DD (40-200 micrograms/kg weight). in hereditary hypertensive rats (ISIAH-strain) significantly (by 30%) decreased systolic arterial blood pressure whereas similar effect of trinitroglycerin was detected at significantly higher dose (900 micrograms/kg weight).