COMPARISON OF INOTROPIC AND ANTIARRHYTHMIC ACTIVITY OF FLAVONOIDS — QUERCETIN, RUTIN AND (+)-CATECHIN

• Published in: Rossiĭskiĭ kardiologicheskiĭ zhurnal no. 11; pp. 35 - 41
• Main Authors: Sh. S. Khushmatov, R. R. Makhmudov, S. M. Mavlyanov
• Format: Journal Article
• Language: Russian
• Published: FIRMA «SILICEA» LLC 01.11.2015
• Subjects: (+)-katechin; apillary muscle; arrhythmia; inotropia; quercetin; rutin
• ISSN: 1560-4071; 2618-7620
• DOI: 10.15829/1560-4071-2015-11-35-41

Aim. Studying of inotropic and antiarrhythmic action of flavonoids — quercetin, rutin and (+)-catechin on functional activity of rodent myocardium.Material and methods. Mechanical parameters of papillary muscle in isometric regimen were registered via the sensor F30, in simulation with the impulses 5-10 ms duration and amplitude, higher than threshold for ~20%. For defining of flavonoids action mechanism we used the inhibitory method of the being studied compounds with ion-transporting system and receptors of cardiomyocytes sarcolemma. To study antiarrhythmic action of flavonoids we used the method of experimental acotinin-induced arrhythmia.Results. It is found that quercetin and rutin have biphasic inotropic effect on contractility of rodent papillary muscle, and rutin leads to significantly lower positive inotropic effect than quercetin. In diapason of higher concentrations quercetin (100-200 mcM) and rutin (200-300) lead just to negative inotropic effect. In such conditions the value of ЕС50 for quercetin and rutin was 229 mcM or pD2 (–log EC50)=3,64 and 245,4 mcM or pD2 (–log EC50)=3,61 resp. It was found that (+)-catechin shows only negative inotropic effect (ЕС50=45,7 mcM and pD2 (–log EC50)=4,34). In incubation of the muscle with (±)-propranolol (10 mcM), blocker of Ἰ-adrenoreceptor, there is a decrease of positive inotropic effect of quercetin and rutin. In experiments we found that in presence of Са2+L-channel antagonist — nifedipine (ЕС50), querctin (229 mcM), rutin (245,4 mcM) and (+)-catechin (45,7 mcM) additionally decreased the amplitude of myocardium contractile response by 41,3±5,4%, 43,6±6,5% and 37,2±4,8%, resp, relatively to nifedipine effect. Revealed, that the studied flavonoids, in 20-25 min after addition to the incubation medium, suppress the rate of arrhythmia, caused by aconitin (1 mcM). Also the most effective was quercetin, and in concentration 100 mcM it decreases the rate of tachycardia, caused by aconitine from от 264±14 bpm to 32±12 bpm.Conclusion. Analyzing the data obtained, it is possible to presume that positive inotropic effect of quercetin and rutin might be related to their activtion of ⊘-andrenoreceptors, which causes the increase of [cAMP]in and, hence leads to increase of intracellular [Ca2+]in in cardiomyocytes. Negative action of the studied flavonoids might be relevant to their interaction with Са2+-channels of cardiomyocytes sarcolemma. Also the action of the flavonoids might be related to the production of functional activity modulation of Na+ and Са2+-channels in cardiomyocytes.