Investigations on the pharmacology of the cardioprotective guanidine ME10092

Maija Dambrova, Edgars Liepinsh, Olga Kirjanova, Ramona Petrovska, Osvalds Pugovich, Larisa Baumane, Staffan Uhlen, Ivars Kalvinsh, Douglas Oliver, Jarl E.S. Wikberg

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)- guanidine), which possesses a strong cardioprotective effect to ischemia-reperfusion, was assessed for different pharmacological actions that may underlie its cardioprotective effect. In the living rat ME10092 decreased the blood pressure and heart rate in a dose-dependent manner. We found ME10092 to bind to α1- and α2-adrenoreceptors with moderate affinity (Ki values 1-4 μM), and to block adrenaline-elicited contractile responses in isolated guinea pig aortas. Our results indicate that ME10092 possesses a certain anti-oxidant profile. Thus, in a competitive manner and with low affinity it inhibited the bovine milk xanthine oxidase enzyme, as well as NAD(P)H oxidase driven oxyradical formation in membrane fractions isolated from the rat brain. By using electron paramagnetic resonance we here show that, after its systemic administration, ME10092 modulates the nitric oxide (NO) content in several tissues of the rat in a time-dependent manner. However, in vitro ME10092 inhibited the activities of nitric oxide synthases nNOS and eNOS, but not that of iNOS. Our data give evidence that the cardioprotective effect of ME10092 could be mediated through pharmacological mechanisms that include some modulation of NO production, as well as possible inhibition of radical formation during ischemia-reperfusion.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue number2
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

Keywords

  • Adrenoreceptor
  • Guanidine
  • NAD(P)H oxidase
  • Nitric oxide synthase
  • Xanthine oxidase

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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