EPR investigation of in vivo inhibitory effect of guanidine compounds on nitric oxide production in rat tissues

Maija Dambrova, O. Kirjanova, L. Baumane, E. Liepinsh, L. Zvejniece, R. Muceniece, I. Kalvinsh, J. E.S. Wikberg

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
1 Downloads (Pure)

Abstract

The aim of the present study was to evaluate in vivo effects on NO production of pharmacologically widely used, commercially available NOS inhibitors, structurally related to guanidine. We compared the NO inhibitory potency and selectivity of L-NAME, aminoguanidine and guanabenz in tissues of normal and LPS-stimulated rats using ex vivo EPR measurements of the NO radical in its complex with dithiocarbamate-Fe(II). The tissues studied were the brain cortex, kidney, liver, heart and testis. Differential inhibitory effects were seen for L-NAME, aminoguanidine and guanabenz when applied during basal or LPS-stimulated conditions. Aminoguanidine exerted inhibition of NO only after stimulation with LPS. Guanabenz had little effect on NO in liver, kidney, testis and heart under normal conditions, while it reduced the basal NO in brain cortex. After stimulation with LPS guanabenz afforded a partial inhibition of the NO formation in all tissues studied. L-NAME was a potent inhibitor of NO synthesis in all tested tissues, both during basal and LPS stimulated conditions. Our results show that compounds containing a guanidine moiety might possess different NOS inhibitory profiles in vivo.

Original languageEnglish
Pages (from-to)339-347
Number of pages9
JournalJournal of Physiology and Pharmacology
Volume54
Issue number3
Publication statusPublished - Sep 2003
Externally publishedYes

Keywords

  • Aminoguanidine
  • EPR
  • Guanabenz
  • L-NAME
  • Nitric oxide

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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