Volchyk I. Search cardioprotective agents among derivatives of 4-amіno-1,2,4-triazole

Thesis is devoted to the study of cardioprotective activity among derivatives of 4-amino-1,2,4-triazole in experimental myocardial infarction and spontaneous hypertension. Established, that from 12 compounds - derivatives of 4-amino-1,2,4-triazole, 8 compounds had cardioprotective and ?-adrenoblocking activity. And compound Hipertryl (1-(?-pheniletyl)-4-amino-1,2,4 triazoliy bromide) significantly exceeds efficiency of metoprolol. Further studies of Hipertryl’s activity found that his assignment a dose 2,5 mg/kg intraperitoneally to animals with myocardial infarction resulted in lower mortality, reduce areas of necrosis, decrease of mitochondrial dysfunction in cardiomyocytes, improvement of the myocardium energy, inhibition of oxidative stress, normalize heart rate, lower total the degree of deviation of the interval ST (??ST) of contours. Hipertryl showed NO-mimetic properties - increased the expression and activity of eNOS, and synthesis of NO. Assigment of Hipertryl in dose of 5 mg/kg to SHR rats resulted in lowering blood pressure, reducing myocardial hypertrophy, normalized system L-arginine-NO-synthase-NO, increased production of NO by expression of eNOS and decrease of nitrosating stress in the myocardium. Hipertryl showed significant antioxidant effect, increasing activity of antioxidant enzymes and inhibiting oxidative modification of proteins.