The state of the myocardial nitrooxidergic system during modelling of doxorubicin-induced chronic heart failure and the administration of βeta-blockers of various generations

Abstract

In this study, a 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) with β-blocker and NO-mimetic properties, which is of interest for the treatment of chronic heart failure (CHF) was examined. The purpose was to study the effect of various β-blockers on the indicators of the NO system in a CHF model. CHF was induced with doxorubicin at a cumulative dose of 14 mg/kg in 85 Wistar rats, which were intragastrically administered metoprolol succinate (15 mg/kg), carvedilol (50 mg/kg), bisoprolol (10 mg/kg), nebivolol (10 mg/kg) and Hypertril (3.5 mg/kg). In the heart, the expression of eNOS and iNOS and the concentration of stable metabolites NO, nitrotyrosine and SH groups were determined. Modelling of CHF leads to a decrease in the expression of eNOS and an increase in iNOS and nitrotyrosine, as well as a deficiency of NO and the SH group. Nebivolol, especially Hypertril, had the most pronounced normalising effect on the NO system. The advantage of Hypertril over basic β-blockers was revealed.