The state of the nucleo-nucleolar apparatus of the mature albino rat males cardiomyocytes exposed to intrauterine hypoxia and neonatal administration of non-opiate analogues of leu-enkephalin

Abstract

Intrauterine hypoxia (IUH) changes the postnatal heart development and contributes to the individual susceptibility to cardiovascular diseases, also by impairment of protein-synthetic function of cardiomyocytes (CMC). Non-opiate analogues of leu-enkephalin, peptides NALE (Phe–D-Ala–Gly–Phe–Leu–Arg) and G (Phe–D-Ala–Gly–Phe–Leu–Gly), cytoprotectors with the wide spectrum of biological activity, improve the state of the CMC nucleo-nucleolar apparatus in neonatal age after IUH. The aim of the study was to analyze the parameters of CMC nucleo-nucleolar apparatus in mature albino rats, exposed to IUH and to the neonatal administration of peptides-analogues of leu-enkephalin. Material and methods. The offspring of Wistar rat females, subjected to hypobaric exposure (15–19 days of gestation, pO2 = 65 mm. Hg, duration – 4 hours), received from day 2 to day 6 of life daily intraperitoneal injections of NALE and G peptides (100 µg/kg), as well as NALE in combination with non-selective NO synthase blocker L-NAME (50 mg/kg), after that they were withdrawn from the experiment in mature age (60 days). The animals of control group and the comparison group received an equal volume of isotonic sodium chloride solution. The karyo- and nucleolometric parameters of CMC, and also the CMC nucleoli number were analyzed in heart sections, stained by using AgNOR method. Results and their discussion. IUH induced the significant decrease in nucleoli number of the CMC of both heart ventricles, and also led to the impairment of karyo- and nucleolometric parameters of the CMC in the mature offspring. Administration of NALE peptide in dose of 100 µg/kg in neonatal period corrected the posthypoxic changes of the CMC nucleonucleolar apparatus. Neonatal administration of non-selective NO-synthase blocker (L-NAME, 50 mg/kg) obviated the registered effects of NALE. The correction of delayed posthypoxic changes, similar to the effects of NALE, was observed after administration of its arginineless analogue– the G peptide. Conclusions. The cardioprotective effect of NALE is partially mediated by L-arginine – a potential donator of nitric oxide. Non-opiate analogues of leu-enkephalin – the NALE and G peptides, might be considered as perspective cardioprotective substances with the delayed activity, preventing the long-term consequences of the IUH.

Keywords

• cardiomyocytes
• intrauterine hypoxia
• nitric oxide
• nucleoli
• non-opiate analogues of leu-enkephalin