Hypobaric hypoxia (pO2 65 mm Hg, duration 4 h) induced a significant increase in the number of cardiomyocytes expressing р53, beclin-1, endothelial NO synthase and accumulation and degranulation of mast cells in the epicardium in hearts of prepubertal female rats (age 45-47 days); the number of cardiomyocytes with nucleoli decreased, while the number of single-nucleolar cardiomyocytes increased after this exposure. Five-fold administration of non-opiate analogue of leu-enkephalin (NALE peptide: Phe–D-Ala–Gly–Phe–Leu–Arg; 100 μg/kg) during the neonatal period reduced the severity of the post-hypoxic changes in the heart. Neonatal administration of NALE (100 μg/kg) against the background of NO synthase blockade with L-NAME (50 mg/kg) did not abolish the cardioprotective effects of the peptide. A similar correction of posthypoxic changes in the heart was observed after neonatal administration of original peptide G (Phe–D-Ala–Gly–Phe–Leu–Gly; 100 μg/kg). Thus, NO synthase—NO system and C-terminal amino acid Arg in the molecule of non-opiate analogue of leu-enkephalin are not required for the cardioprotective effects of peptides. Non-opiate leu-enkephalin analogs, peptides NALE and G, can be considered as promising substances for increasing heart resistance to hypoxia during later age periods.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Krylatov AV, Vaizova OE, Belousov MV, Poznyakova SV, Madonov PG. Role of opioid receptors in the regulation of resistance of heart to impact of ischemia-reperfusion. Ross. Fiziol. Zh. Im I. M. Sechenova. 2017;103(3):230-249. Russian.
Khaytsev NV, Vasiliev AG, Trashkov AP, Kravtsova AA, Balashov LD. The influence of sex and age upon response of white rats to hypoxic hypoxia. Pediatr. 2015;6(2):71-77. Russian.
Avitabile D, Bailey B, Cottage CT, Sundararaman B, Joyo A, McGregor M, Gude N, Truffa S, Zarrabi A, Konstandin M, Khan M, Mohsin S, Völkers M, Toko H, Mason M, Cheng Z, Din S, Alvarez R Jr, Fischer K, Sussman MA. Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucle-ostemin and nucleophosmin. Proc. Natl Acad. Sci. USA. 2011;108(15):6145-6150. doi: https://doi.org/10.1073/pnas.1017935108
Gong N, Yang X, Li X, Jiang Y, Gu C, Ma S, Gao Q, Cheng X. MicroRNA-590-3p relieves hypoxia/reoxygenation induced cardiomyocytes apoptosis and autophagy by targeting HIF-1α. Exp. Ther. Med. 2021;22(4):1077. doi: https://doi.org/10.3892/etm.2021.10511
Ghafourifar P, Cadenas E. Mitochondrial nitric oxide synthase. Trends Pharmacol. Sci. 2005;26(4):190-195. doi: https://doi.org/10.1016/j.tips.2005.02.005
Ikeda M, Ide T, Tadokoro T, Miyamoto HD, Ikeda S, Okabe K, Ishikita A, Sato M, Abe K, Furusawa S, Ishimaru K, Matsushima S, Tsutsui H. Excessive Hypoxia-Inducible Factor-1α Expression Induces Cardiac Rupture via p53-Dependent Apoptosis After Myocardial Infarction. J. Am. Heart. Assoc. 2021;10(17):e020895. doi: https://doi.org/10.1161/JAHA.121.020895
Kareinen I, Baumann M, Nguyen SD, Maaninka K, Anisimov A, Tozuka M, Jauhiainen M, Lee-Rueckert M, Kovanen PT. Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I at Tyr192 and compromises its cardioprotective activity. J. Lipid. Res. 2018;59(6):945-957. doi: https://doi.org/10.1194/jlr.M077503
Minato H, Hisatome I, Kurata Y, Notsu T, Nakasone N, Ninomiya H, Hamada T, Tomomori T, Okamura A, Miake J, Tsuneto M, Shirayoshi Y, Endo R, Otsuki A, Okada F, Inagaki Y. Pretreatment with cilnidipine attenuates hypoxia/reoxygenation injury in HL-1 cardiomyocytes through enhanced NO production and action potential shortening. Hypertens. Res. 2020;43(5):380-388. doi: https://doi.org/10.1038/s41440-019-0391-7
Naryzhnaya NV, Khaliulin I, Lishmanov YB, Suleiman MS, Tsibulnikov SY, Kolar F, Maslov LN. Participation of opioid receptors in the cytoprotective effect of chronic normobaric hypoxia. Physiol. Res. 2019;68(2):245-253. doi: https://doi.org/10.33549/physiolres.933938
Oyamada S, Bianchi C, Takai S, Chu LM, Sellke FW. Chymase inhibition reduces infarction and matrix metal-loproteinase-9 activation and attenuates inflammation and fibrosis after acute myocardial ischemia/reperfusion. J. Pharmacol. Exp. Ther. 2011;339(1):143-151. doi: https://doi.org/10.1124/jpet.111.179697
Palmer CB, Meyrath M, Canals M, Kostenis E, Chevigné A, Szpakowska M. Atypical opioid receptors: unconventional biology and therapeutic opportunities. Pharmacol. Ther. 2021:108014. doi: https://doi.org/10.1016/j.pharmthera.2021.108014
Reid AC, Brazin JA, Morrey C, Silver RB, Levi R. Targeting cardiac mast cells: pharmacological modulation of the local renin-angiotensin system. Curr. Pharm. Des. 2011;17(34):3744-3752. doi: https://doi.org/10.2174/138161211798357908
Sazonova EN, Tcimbalist NA, Kaplieva OV, Lebed’ko OA. The influence of non-opiate analogue of leu-enkephalin to the cardiac consequences of intrauterine hypoxia of albino rats. Russ. Open Med. J. 2019;8(4):401. doi: https://doi.org/10.15275/rusomj.2019.0401
Toll L, Bruchas MR, Calo’ G, Cox BM, Zaveri NT. Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems. Pharmacol. Rev. 2016;68(2):419-457. doi: https://doi.org/10.1124/pr.114.009209
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 173, No. 2, pp. 158-163, February, 2022
Rights and permissions
About this article
Cite this article
Sazonova, E.N., Gusev, I.A., Malofey, Y.B. et al. Effects of Neonatal Administration of Non-Opiate Analogues of Leu-Enkephalin to Heart Tissue Homeostasis of Prepubertal Albino Rats Exposed to Hypoxia. Bull Exp Biol Med 173, 188–192 (2022). https://doi.org/10.1007/s10517-022-05516-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-022-05516-0