Effects of Neonatal Administration of Non-Opiate Analogues of Leu-Enkephalin on the Delayed Cardiac Consequences of Intrauterine Hypoxia.

Intrauterine hypoxia (gestation days 15-19, pO₂ 65 mm Hg, duration 4 h) led to an increase in the expression of p53, beclin-1, endothelial NO synthase (eNOS), and caspase-3 proteins in cardiomyocytes and reduced the number of mast cells in the heart of 60-day-old albino rats. Administration of a non-opiate analogue of leu-enkephalin (NALE peptide: Phe-D-Ala-Gly-Phe-Leu-Arg, 100 μg/kg) on days 2-6 of the neonatal period decreased the severity of delayed posthypoxic myocardial reaction. The content of eNOS⁺ cardiomyocytes and the total number of mast cells of these animals did not differ from the control parameters; the content of p53⁺ cardiomyocytes was significantly lower than in animals exposed to intrauterine hypoxia. The cardioprotective activity of NALE was partially neutralized by co-administration with the NO synthase inhibitor (L-NAME, 50 mg/kg). Correction of the delayed posthypoxic changes, similar to the effects of NALE peptide, was observed after neonatal administration of its arginine-free analogue, G peptide (Phe-D-Ala-Gly-Phe-Leu-Gly; 100 μg/kg). Non-opiate analogues of leu-enkephalin NALE and G peptides can be considered as promising substances capable of preventing long-term cardiac consequences of intrauterine hypoxia.