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.
Similar content being viewed by others
REFERENCES
Berend K, de Vries APJ, Gans ROB (2014) Physiological Approach to Assessment of Acid–Base Disturbances. N Engl J Med 371: 1434–1445.https://doi.org/10.1056/NEJMRA1003327/SUPPL_FILE/NEJMRA1003327_DISCLOSURES.PDF
Gainullina DK, Shvetsova AA, Tarasova OS (2022) Mechanisms of the influence of acidosis on the tone of blood vessels. Aerospace Environment Med 56: 38–45.https://doi.org/10.21687/0233-528x-2022-56-5-38-45
Gaynullina DK, Tarasova OS, Shvetsova AA, Borzykh AA, Schubert R (2022) The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis. Int J Mol Sci 23: 5987.https://doi.org/10.3390/ijms23115987
Boedtkjer E, Aalkjaer C (2012) Intracellular pH in the resistance vasculature: regulation and functional implications. J Vasc Res 49: 479–496.https://doi.org/10.1159/000341235
Boedtkjer E (2018) Acid–base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone. J Cereb Blood Flow Metab 38: 588–602.https://doi.org/10.1177/0271678X17733868
Remzső G, Németh J, Varga V, Kovács V, Tóth-Szűki V, Kaila K, Voipio J, Domoki F (2020) Brain interstitial pH changes in the subacute phase of hypoxic-ischemic encephalopathy in newborn pigs. PLoS One 15: e0233851.https://doi.org/10.1371/journal.pone.0233851
Shvetsova AA, Gaynullina DK, Tarasova OS, Schubert R (2019) Negative feedback regulation of vasocontraction by potassium channels in 10- to 15-day-old rats: Dominating role of Kv7 channels. Acta Physiol 225: e13176.https://doi.org/10.1111/apha.13176
Wang X, Wu J, Li L, Chen F, Wang R, Jiang C (2003) Hypercapnic acidosis activates KATP channels in vascular smooth muscles. Circ Res 92: 1225–1232.https://doi.org/10.1161/01.RES.0000075601.95738.6D
Celotto AC, Restini CBA, Capellini VK, Bendhack LM, Evora PRB (2011) Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta. Eur J Pharmacol 656: 88–93.https://doi.org/10.1016/j.ejphar.2011.01.053
Lindauer U, Vogt J, Schuh-Hofer S, Dreier JP, Dirnagl U (2003) Cerebrovascular Vasodilation to Extraluminal Acidosis Occurs via Combined Activation of ATP-Sensitive and Ca2+-Activated Potassium Channels. J Cereb Blood Flow Metab 23(10): 1227–1238.https://doi.org/10.1097/01.WCB.0000088764.02615.B7
Rohra DK, Sharif HM, Zubairi HS, Sarfraz K, Ghayur MN, Gilani AH (2005) Acidosis-induced relaxation of human internal mammary artery is due to activation of ATP-sensitive potassium channels. Eur J Pharmacol 514: 175–181.https://doi.org/10.1016/j.ejphar.2005.02.041
Phillis JW, Song D, O’Regan MH (2000) Mechanisms involved in coronary artery dilatation during respiratory acidosis in the isolated perfused rat heart. Basic Res Cardiol 95: 93–97.https://doi.org/10.1007/s003950050169
Gurney A, Manoury B (2009) Two-pore potassium channels in the cardiovascular system. Eur Biophys J 38: 305–318.https://doi.org/10.1007/s00249-008-0326-8
Goldstein SAN, Bockenhauer D, O’Kelly I, Zilberberg N (2001) Potassium leak channels and the KCNK family of two-p-domain subunits. Nat Rev Neurosci 23(2): 175–184.https://doi.org/10.1038/35058574
Olschewski A, Li Y, Tang B, Hanze J, Eul B, Bohle RM, Wilhelm J, Morty RE, Brau ME, Weir EK, Kwapiszewska G, Klepetko W, Seeger W, Olschewski H (2006) Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circ Res 98: 1072–1080.https://doi.org/10.1161/01.RES.0000219677.12988.e9
Antigny F, Hautefort A, Meloche J, Belacel-Ouari M, Manoury B, Rucker-Martin C, Péchoux C, Potus F, Nadeau V, Tremblay E, Ruffenach G, Bourgeois A, Dorfmüller P, Breuils-Bonnet S, Fadel E, Ranchoux B, Jourdon P, Girerd B, Montani D, Provencher S, Bonnet S, Simonneau G, Humbert M, Perros F (2016) Potassium channel subfamily K member 3 (KCNK3) contributes to the development of pulmonary arterial hypertension. Circulation 133: 1371–1385.https://doi.org/10.1161/CIRCULATIONAHA.115.020951
Gardener MJ, Johnson IT, Burnham MP, Edwards G, Heagerty AM, Weston AH (2004) Functional evidence of a role for two-pore domain potassium channels in rat mesenteric and pulmonary arteries. Br J Pharmacol 142: 192–202.https://doi.org/10.1038/sj.bjp.0705691
Shvetsova AA, Gaynullina DK, Schmidt N, Bugert P, Lukoshkova EV, Tarasova OS, Schubert R (2020) TASK-1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1- to 2-week-old but not adult rats. Br J Pharmacol 177: 5148–5162.https://doi.org/10.1111/bph.15249
Stulcova B (1977) Postnatal development of cardiac output distribution measured by radioactive microspheres in rats. Neonatology 32: 119–124.
Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41: 19–26.https://doi.org/10.1161/01.RES.41.1.19
Yartsev VN, Karachentseva OV, Dvoretsky DP (2002) Effect of pH changes on reactivity of rat mesenteric artery segments at different magnitude of stretch. Acta Physiol Scand 174: 1–7.https://doi.org/10.1046/j.1365-201x.2002.00923.x
Mohanty I, Suklabaidya S, Parija SC (2016) Acidosis reduces the function and expression of α1D-adrenoceptor in superior mesenteric artery of capra hircus. Int J Pharmacol 48: 399–406.https://doi.org/10.4103/0253-7613.186199
Aoyama Y, Ueda K, Setogawa A, Kawai Y (1999) Effects of pH on contraction and Ca2+ mobilization in vascular smooth muscles of the rabbit basilar artery. Jpn J Physiol 49: 55–62.
Akanji O, Weinzierl N, Schubert R, Schilling L (2019) Acid sensing ion channels in rat cerebral arteries: Probing the expression pattern and vasomotor activity. Life Sci 227: 193–200.https://doi.org/10.1016/j.lfs.2019.04.054
Aleksandrowicz M, Kozniewska E (2020) Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia. Microcirculation 27: 1–7.https://doi.org/10.1111/micc.12644
Hessellund A, Aalkjaer C, Bek T (2006) Effect of acidosis on isolated porcine retinal vessels. Curr Eye Res 31: 427–434.https://doi.org/10.1080/02713680600681236
Ives SJ, Andtbacka RHI, Noyes RD, Morgan RG, Gifford JR, Park SY, Symons JD, Richardson RS (2013) α1-Adrenergic responsiveness in human skeletal muscle feed arteries: The impact of reducing extracellular pH. Exp Physiol 98: 256–267.https://doi.org/10.1113/expphysiol.2012.066613
Nakanishi T, Gu H, Momma K (1997) Developmental changes in the effect of acidosis on contraction, intracellular pH, and calcium in the rabbit mesenteric small artery. Pediatr Res 42: 750–757.https://doi.org/10.1203/00006450-199712000-00006
Nakanishi T, Gu H, Momma K (1997) Effect of acidosis on contraction, intracellular pH, and calcium in the newborn and adult rabbit aorta. Heart Vessels 12: 207–215.https://doi.org/10.1007/BF02766785
Lotshaw DP (2007) Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ hannels. Cell Biochem Biophys 47(2): 209–256.https://doi.org/10.1007/s12013-007-0007-8
Ma L, Zhang X, Zhou M, Chen H (2012) Acid-sensitive TWIK and TASK Two-pore Domain Potassium Channels Change Ion Selectivity and Become Permeable to Sodium in Extracellular Acidification. J Biol Chem 287(44): 37145–37153.https://doi.org/10.1074/jbc.M112.398164
Mochalov SV, Tarasova NV, Kudryashova TV, Gaynullina DK, Kalenchuk VU, Borovik AS, Vorotnikov AV, Tarasova OS, Schubert R (2018) Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity. Acta Physiol 223: 1–15.https://doi.org/10.1111/apha.13044
Akopov SE, Zhang L, Pearce WJ (1998) Regulation of Ca2+ sensitization by PKC and rho proteins in ovine cerebral arteries: Effects of artery size and age. Am J Physiol - Hear Circ Physiol 275: 930–939.https://doi.org/10.1152/ajpheart.1998.275.3.h930
Boedtkjer E, Praetorius J, Matchkov VV, Stankevicius E, Mogensen S, Füchtbauer AC, Simonsen U, Füchtbauer EM, Aalkjaer C (2011) Disruption of Na+, HCO2 – cotransporter NBCn1 (slc4a7) Inhibits no-mediated vasorelaxation, smooth muscle Ca2+ Sensitivity, and hypertension development in mice. Circulation 124: 1819–1829.https://doi.org/10.1161/CIRCULATIONAHA.110.015974
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.
Author information
Authors and Affiliations
Contributions
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.).
Corresponding author
Ethics declarations
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).
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
Additional information
Translated by A. Polyanovsky
Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1134/S0022093024010174