Upregulation of ATP-Sensitive Potassium Channels as the Potential Mechanism of Cardioprotection and Vasorelaxation Under the Action of Pyridoxal-5-Phosphate in Old Rats

Autor: Ruslan B. Strutynskyi PhD, DSc, Nataliіa A. Strutynska PhD, Oksana O. Piven PhD, DSc, Lidiia A. Mys PhD, Yulia V. Goshovska PhD, Raisa A. Fedichkina PhD, Iryna Y. Okhai (postgraduate), Vladyslav R. Strutynskyi PhD student, Victor E. Dosenko MD, PhD, DSc, Pawel Dobrzyn PhD, DSc, Vadim F. Sagach MD, PhD, DSc
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cardiovascular Pharmacology and Therapeutics, Vol 28 (2023)
Druh dokumentu: article
ISSN: 1940-4034
10742484
DOI: 10.1177/10742484231213175
Popis: Background: The aging process is accompanied by the weakening of the protective systems of the organism, in particular by the decrease in the expression of ATP-sensitive potassium (K ATP ) channels and in the synthesis of H 2 S. The aim of our work was to investigate the role of K ATP channels in the cardioprotection induced by pyridoxal-5-phosphate (PLP) in aging. Methods: Experiments were performed on adult and old (aged 24 months) male Wistar rats, which were divided into 3 groups: adults, old, and old PLP-treated rats. PLP was administered orally once a day for 14 days at a dose of 0.7 mg/kg. The levels of mRNA expression of subunits K ATP channels were determined by reverse transcription and real-time polymerase chain reaction analysis. Protein expression levels were determined by the Western blot. Cardiac tissue morphology was determined using transverse 6 μm deparaffinized sections stained with picrosirius red staining. Vasorelaxation responses of isolated aortic rings and the function of Langendorff-perfused isolated hearts during ischemia-reperfusion, H 2 S levels, and markers of oxidative stress were also studied. Results: Administration of PLP to old rats reduces cardiac fibrosis and improves cardiac function during ischemia-reperfusion and vasorelaxation responses to K ATP channels opening. At the same time, there was a significant increase in mRNA and protein expression of SUR2 and Kir6.1 subunits of K ATP channels, H 2 S production, and reduced markers of oxidative stress. The specific K ATP channel inhibitor—glibenclamide prevented the enhancement of vasodilator responses and anti-ischemic protection in PLP-treated animals. Conclusions: We suggest that this potential therapeutic effect of PLP in old animals may be a result of increased expression of K ATP channels and H 2 S production.
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