INFLUENCE OF AFOBAZOL ON THE LEVEL OF INDUCIBLE NO-SYNTHASE IN ISCHEMIC MYOCARDIUM

DOI: https://doi.org/None

S.A. Kryzhanovskii, T.A. Antipova, I.B. Tsorin, S.V. Kruglov, E.O. Ionova, V.N. Stolyaruk, M.B. Vititnova Research Zakusov Institute of Pharmacology, Baltiyskaya st., 8, Moscow, 125315, Russian Federation

The purpose of this study. Evaluation the effect of Afobazol on the level of myocardial inducible NO-synthase (iNOS) in the ischemic myocardium in rats. Methods. Myocardial ischemia was produced by the Selye’s method. The of inducible NO-synthase level on the 15th day after coronary artery ligation was determined with the use of Western blot analysis with specific antibodies against this protein. On the 2nd and the 14th day after the coronary artery ligation the state of the intracardiac hemodynamics was assessed with the use of echocardiography. Results. Inducible NO-synthase levels in the myocardium by Afobazol post-ischemia treatment (15 mkg/kg i.p., 14 days) were shown to be unchanged if compared with the level of iNOS in the intact animals (2,03±0,26 vs. 2,21±0,29 relative density units, respectively), and to be significantly lower (2,03±0,26 vs. 3,22±0,28 relative density units, respectively; p≈0,019) than in the ischemic control group. The echocardiographic studies data demonstrated that experimental therapy with Afobazol (statistic significantly compared to the control) restored cardiac pump function of the rats with myocardial infarct. Thus, if in control animals from the 2nd to the 14th day after the reproduction of myocardial infarction the ejection fraction dynamically decreased from 64,7±3,6% up to 52,9±3,0%, then Afobazol-treated animals, it is, on the contrary, showed a clear trend to recovery from 57,8±3,0%, to 61,1±3,4% (p≈0,007). Conclusion. In the present study, for the first there was demonstrated the ability of agonists of σ1-receptors, in particular afobazol, to prevent or decrease expression of iNOS in ischemic myocardial tissue. Earlier, the same data were shown only for ischemic neurons, what was considered as one of the causes of antiischemic (neuroprotective) activity of Afobazol.
Keywords: 
myocardial ischemia, agonist of σ1-receptors, inducible NO-synthase, echocardiograpy, intracardiac hemodynamics

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