Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium

• Published in: Fiziolohichnyi zhurnal (Kiev, Ukraine : 1994) Ukraine : 1994), 2013, Vol.59 (4), p.16-27
• Main Authors: Strutyns'kyĭ, R B, Kotsiuruba, A V, Rovenets', R A, Strutyns'ka, N A, Iagupols'kyĭ, Iu L, Sagach, V F, Moĭbenko, O O
• Format: Article
• Language: eng ; ukr
• Subjects: Animals; Apoptosis - drug effects; Arginase - antagonists & inhibitors; Arginase - metabolism; Cardiotonic Agents - pharmacology; Dogs; Heart - drug effects; Heart - physiopathology; Heme Oxygenase (Decyclizing) - antagonists & inhibitors; Heme Oxygenase (Decyclizing) - metabolism; Hydroxyl Radical - antagonists & inhibitors; Lipoxygenase - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - antagonists & inhibitors; Mitochondrial Membrane Transport Proteins - metabolism; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Nitric Oxide - metabolism; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Peroxynitrous Acid - antagonists & inhibitors; Pinacidil - analogs & derivatives; Pinacidil - pharmacology; Tablets; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism
• ISSN: 2522-9028; 2522-9036
• DOI: 10.15407/fz59.04.016

In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) of myocardium it was investigated changes of biochemical processes in arterial blood at intragastric introduction of medicinal form (tablets) of flocalin (the fluorine-containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The data analysis allowed to define a few possible mechanisms of cardioprotective action offlocalin, which prevented the opening of a mitochondrial permeability transition pore (MPTP) and inhibition of apoptosis induced by it. They consist, from one side, in activating of the constitutive de novo biosynthesis of nitric oxide by cNOS, from other side, in suppression of inducible nitric oxide de novo synthesis by iNOS in such way to prevent the formation of toxic peroxynitrite by co-operation of surplus nitric oxide with superoxide anion, thereby limits the generation of toxic active forms of nitrogen (*NO2) and oxygen (*OH). The first effect of flocalin takes place due to limitation the degradation of L-arginine by arginase which keeps substrat for cNOS, second--due to the inhibition of superoxide generation, in particular, by xanthine oxidase (marker uric acid), lipoxigenase (marker LTC4) and cyclooxygenase (marker TxB2). Because LTC4 have coronaroconstrictory, arrhythmogenic and chemoattractory properties in the conditions of myocardial ischemia, inhibition of its production both with superoxide generation (markers H2O2 and diene conjugates) may be the another mechanisms of flocalin's cardioprotection. Powerful antiischemic action of flocalin (marker nitrite anion) as the mechanisms of cardioprotection is possible as well as inhibition of ATP and GTP degradation (marker hypoxanthine+xanthine+inosine levels in the blood) and, possibly, stimulation ofhaem degradation by haem oxygenase (markers total bilirubin and Fe in the blood). Diminishing content of free arachidonic acid in arterial blood can testify inhibition of cellular membranes phospholipides degradation by phospholipase A2 as a result of flocalin cardioprotection.