Effect of combination of zafirlukast and quercetin on baroreflex sensitivity and endothelin production in rats with myocardial infarction.
The purpose of this study was to evaluate the influence of zafirlukast (Z), quercetin (Q) and their combination on baroreflex sensitivity (BRS), endothelin-1 (E1) plasma concentration and the severity of ventricular arrhythmias (VA) occurring during myocardial infarction (MI). In anaesthetized Wistar rats, MI was induced by ligation of the left anterior descending coronary artery (CAL). Animals were divided into the five groups: I--sham-operated (SO); II--CAL; III--CAL+Z (0.25 mg/kg intraperitoneally 1 hour prior and 12-24 hour after CAL); IV--CAL+Q (1.5 mg/kg by i.v. injection after anesthesia and every 24 hour during 72 hour); V--CAL+Z+Q as above. CAL after 1 hour was accompanied by high incidence of VA associated with a significant mortality (68% at 72 hour) as compared with SO rats. In survived rats BRS was greatly attenuated (0.44 +/- 0.08 ms/mmHg) vs. SO animals (0.92 +/- 0.14 ms/mmHg, p < 0.05) that correlated to increase E1 plasma concentration (9.2 +/- 0.6 pg/ml) vs. SO rats (2.9 +/- 0.4 pg/ml, p < 0.001). Q did not influence markedly on the severity of VA or rats mortality, while Z and Z+Q decreased mortality in rats in compare to II group of animals (from 68%-42% and 30%), increased the reduced BRS resulting from MI (+38.5% and +55.4%, p < 0.05) and blunted the increase of E1 (-34.8% and -43.5% respectively, p < 0.05). Our results suggested a possible beneficial combine action of Z and Q on MI.
Kezeli
T
T
Department of Pharmacology, Faculty of Medicine, State University, Tiflis, Georgia.
Gongadze
N
N
Chapichadze
Z
Z
Bakuridze
K
K
Chirakadze
K
K
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D017704:Baroreflex / Q000187:drug effects*; D004359:Drug Therapy, Combination; D019332:Endothelin-1 / Q000097:blood / Q000187:drug effects; D007211:Indoles; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D048448:Phenylcarbamates; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D019332:Endothelin-1; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D011794:Quercetin; C062735:zafirlukast