Kinetics of Nitric Oxide Liberation by 3,4-Dihydro-1,2-Diazete 1,2-Dioxides and Their Vasodilatory Properties in Vitro and in Vivo

D. I. Utepbergenov, V. V. Khramtsov, L. P. Vlassenko, A. L. Markel, D. G. Mazhukin, A. Y. Tikhonov, L. B. Volodarsky

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23 Citations (Scopus)

Abstract

Derivatives of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD) have been investigated as NO donors in vitro and in vivo. Using nitronylnitroxides as spin traps for NO, these compounds were shown to decompose in water solutions al physiological pH and temperature, producing two molecules of NO per one DD molecule. Rate constants of DD decomposition were found to be in the range from 10-8 to 6.5×10-7 c(-1) in water and between 3×10-7 and 1.6×10-5 c-1 in dimethylsulfoxide. In vitro experiments performed with perfused rat tail artery showed that some of DD derivatives are highly effective vasodilators in concentrations from 5 to 80 μM while standard NO donor 3-(4-morpholino)-sydnonimine, SIN-1, does not lead to arterial vasodilatation in these concentrations. Significant (up to 30%) decrease of systolic arterial blood pressure was observed in hereditary hypertensive rats (ISIAH-strain) when some of DD were injected intraperitoneally in doses 40-200 μ/kg b.w., while the same effect of trinitroglycerin, TNG, was found at much higher dose equal to 900 μg/kg b.w.

Original languageEnglish
Pages (from-to)1023-1032
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume214
Issue number3
DOIs
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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