Please use this identifier to cite or link to this item: 10.1097/00005344-200408000-00006
Title: Investigations on the pharmacology of the cardioprotective guanidine ME10092
Authors: Dambrova, Maija
Liepinsh, Edgars
Kirjanova, Olga
Petrovska, Ramona
Pugovich, Osvalds
Baumane, Larisa
Uhlen, Staffan
Kalvinsh, Ivars
Oliver, Douglas
Wikberg, Jarl E.S.
Keywords: Adrenoreceptor;Guanidine;NAD(P)H oxidase;Nitric oxide synthase;Xanthine oxidase;3.1 Basic medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Pharmacology;Cardiology and Cardiovascular Medicine
Issue Date: Aug-2004
Citation: Dambrova , M , Liepinsh , E , Kirjanova , O , Petrovska , R , Pugovich , O , Baumane , L , Uhlen , S , Kalvinsh , I , Oliver , D & Wikberg , J E S 2004 , ' Investigations on the pharmacology of the cardioprotective guanidine ME10092 ' , Journal of Cardiovascular Pharmacology , vol. 44 , no. 2 , pp. 178-186 . https://doi.org/10.1097/00005344-200408000-00006
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.
DOI: 10.1097/00005344-200408000-00006
ISSN: 0160-2446
Appears in Collections:Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure

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