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Effect of Extracellular Acidosis on Functional Contribution of KATP and TASK-1 Potassium Channels to Vascular Tone Regulation in Early Postnatal Ontogenesis

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Abstract

Activity of many proteins and hence of the mechanisms of vascular tone regulation depend on medium acidity. A decrease of pH (in uncompensated acidosis) typically causes vasorelaxation of blood vessels, which is studied in sufficient detail in an adult organism. However, the effect of acidosis on the mechanisms of vascular tone regulation in the early postnatal period remains almost completely unexplored. The aim of this work was to study the effect of extracellular metabolic acidosis on the functional contribution of KATP and TASK-1 potassium channels to vascular tone regulation in the early postnatal period. We modeled uncompensated extracellular metabolic acidosis (pH 6.8, equimolar NaHCO3 substitution in a solution for NaCl) and studied isometric contractile responses of the saphenous artery in adult rats aged 3–4 months and rat pups aged 12–15 days. Arterial contraction to the α1-adrenergic agonist methoxamine at pH 6.8 was reduced compared to normal pH 7.4 in both 3–4-month- and 12–15-day-old rats. The KATP channel blocker glibenclamide did not alter arterial responses to methoxamine at either pH 7.4 or pH 6.8 in both age groups. The TASK-1 channel blocker AVE1231 did not alter arterial contractile responses at any pH in 3–4-month-old rats. However, in 12–15-day-old rat pups, the AVE1231-induced increase in contractile responses to methoxamine was less at pH 6.8 than at pH 7.4. Thus, acidosis reduces arterial contractile activity in both 3–4-month-old rats and animals in early postnatal ontogenesis, while in the latter, the anticontractile role of TASK-1 channels decreases, and KATP channels do not affect vascular tone regulation at either normal or acidic pH values in any of the age groups.

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ACKNOWLEDGMENTS

The authors are grateful to Prof. Rudolf Schubert (University of Augsburg, Germany) for helpful advice and discussion of the study design and interpretation of the data obtained. A part of the equipment used in the study was provided by Lomonosov Moscow State University within the framework of Federal project “The development of infrastructure for science and education” (Agreement no. 161).

Funding

This work was supported by the Russian Science Foundation (project No. 21-75-10036). No additional grants to carry out or supervise this particular research were obtained.

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Conceptualization and experimental design (A.A.Sh., D.K.G.), data collection (A.A.Sh., A.A.B., D.K.G.), data processing (A.A.Sh., D.K.G.), writing and editing the manuscript (A.A.Sh., D.K.G.).

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Correspondence to D. K. Gaynullina.

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ETHICS APPROVAL

The experiments with animals were carried out in compliance with the NIH Guidelines for the care and use of laboratory animals (http://oacu.od.nih.gov/regs/index.htm) and were approved by the Bioethics Committee of Lomonosov Moscow State University (Minutes No. 97-g-2 dated November 11, 2021).

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The authors declare that they have no conflict of interest.

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Translated by A. Polyanovsky

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Shvetsova, А.A., Borzykh, A.A. & Gaynullina, D.K. Effect of Extracellular Acidosis on Functional Contribution of KATP and TASK-1 Potassium Channels to Vascular Tone Regulation in Early Postnatal Ontogenesis. J Evol Biochem Phys 60, 247–255 (2024). https://doi.org/10.1134/S0022093024010174

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