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

Abstract

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 H₂S. 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, H₂S 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, H₂S 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 H₂S production.