{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:32:50Z","timestamp":1789594370241,"version":"build-2803163510"},"reference-count":118,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-75-10036"],"award-info":[{"award-number":["21-75-10036"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The activity of many vasomotor signaling pathways strongly depends on extracellular\/intracellular pH. Nitric oxide (NO) is one of the most important vasodilators produced by the endothelium. In this review, we present evidence that in most vascular beds of mature mammalian organisms metabolic or respiratory acidosis increases functional endothelial NO-synthase (eNOS) activity, despite the observation that direct effects of low pH on eNOS enzymatic activity are inhibitory. This can be explained by the fact that acidosis increases the activity of signaling pathways that positively regulate eNOS activity. The role of NO in the regulation of vascular tone is greater in early postnatal ontogenesis compared to adulthood. Importantly, in early postnatal ontogenesis acidosis also augments functional eNOS activity and its contribution to the regulation of arterial contractility. Therefore, the effect of acidosis on total peripheral resistance in neonates may be stronger than in adults and can be one of the reasons for an undesirable decrease in blood pressure during neonatal asphyxia. The latter, however, should be proven in future studies.<\/jats:p>","DOI":"10.3390\/ijms23115987","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T08:50:22Z","timestamp":1653555022000},"page":"5987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Dina K.","family":"Gaynullina","sequence":"first","affiliation":[{"name":"Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4230-3849","authenticated-orcid":false,"given":"Olga S.","family":"Tarasova","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Laboratory of Exercise Physiology, State Research Center of the Russian Federation-Institute for Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A.","family":"Shvetsova","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3763-5953","authenticated-orcid":false,"given":"Anna A.","family":"Borzykh","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Laboratory of Exercise Physiology, State Research Center of the Russian Federation-Institute for Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-1461","authenticated-orcid":false,"given":"Rudolf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Physiology, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1159\/000341235","article-title":"Intracellular pH in the resistance vasculature: Regulation and functional implications","volume":"49","author":"Boedtkjer","year":"2012","journal-title":"J. Vasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1177\/0271678X17733868","article-title":"Acid\u2013base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone","volume":"38","author":"Boedtkjer","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1161\/01.RES.76.2.269","article-title":"Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries","volume":"76","author":"Tian","year":"1995","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.mehy.2012.04.031","article-title":"How metabolic acidosis and oxidative stress alone and interacting may increase the risk of fracture in diabetic subjects","volume":"79","author":"Frassetto","year":"2012","journal-title":"Med. Hypotheses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114019","DOI":"10.1016\/j.bcp.2020.114019","article-title":"Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside","volume":"178","author":"Mateuszuk","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119082","DOI":"10.1016\/j.bbamcr.2021.119082","article-title":"Nicotinamide N-methyltransferase in endothelium protects against oxidant stress-induced endothelial injury","volume":"1868","author":"Campagna","year":"2021","journal-title":"Biochim. Biophys. Acta\u2014Mol. Cell Res."},{"key":"ref_7","first-page":"4678252","article-title":"Bardoxolone Methyl Displays Detrimental Effects on Endothelial Bioenergetics, Suppresses Endothelial ET-1 Release, and Increases Endothelial Permeability in Human Microvascular Endothelium","volume":"2020","author":"Stojak","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Aldosari, S., Awad, M., Harrington, E.O., Sellke, F.W., and Abid, M.R. (2018). Subcellular reactive oxygen species (ROS) in cardiovascular pathophysiology. Antioxidants, 7.","DOI":"10.3390\/antiox7010014"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.0001-6772.2003.01174.x","article-title":"Mechanism of acidic pH-induced contraction in spontaneously hypertensive rat aorta: Role of Ca2+ release from the sarcoplasmic reticulum","volume":"179","author":"Rohra","year":"2003","journal-title":"Acta Physiol. Scand."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ma, Z., Qi, J., Fu, Z., Ling, M., Li, L., and Zhang, Y. (2013). Protective Role of Acidic pH-Activated Chloride Channel in Severe Acidosis-Induced Contraction from the Aorta of Spontaneously Hypertensive Rats. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061018"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1007\/S10016-006-9109-9","article-title":"Acidosis augments myogenic constriction in rat coronary arteries","volume":"20","author":"Baxter","year":"2006","journal-title":"Ann. Vasc. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1113\/expphysiol.2014.078634","article-title":"Extracellular acidosis contracts coronary but neither renal nor mesenteric artery via modulation of H+,K+-ATPase, voltage-gated K+ channels and L-type Ca2+ channels","volume":"99","author":"Niu","year":"2014","journal-title":"Exp. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-201x.2002.00923.x","article-title":"Effect of pH changes on reactivity of rat mesenteric artery segments at different magnitude of stretch","volume":"174","author":"Yartsev","year":"2002","journal-title":"Acta Physiol. Scand."},{"key":"ref_14","first-page":"399","article-title":"Acidosis reduces the function and expression of \u03b11D-adrenoceptor in superior mesenteric artery of capra hircus","volume":"48","author":"Mohanty","year":"2016","journal-title":"Int. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2170\/jjphysiol.49.55","article-title":"Effects of pH on contraction and Ca2+ mobilization in vascular smooth muscles of the rabbit basilar artery","volume":"49","author":"Aoyama","year":"1999","journal-title":"Jpn. J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.lfs.2019.04.054","article-title":"Acid sensing ion channels in rat cerebral arteries: Probing the expression pattern and vasomotor activity","volume":"227","author":"Akanji","year":"2019","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12644","DOI":"10.1111\/micc.12644","article-title":"Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia","volume":"27","author":"Aleksandrowicz","year":"2020","journal-title":"Microcirculation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/02713680600681236","article-title":"Effect of acidosis on isolated porcine retinal vessels","volume":"31","author":"Hessellund","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejphar.2005.02.041","article-title":"Acidosis-induced relaxation of human internal mammary artery is due to activation of ATP-sensitive potassium channels","volume":"514","author":"Rohra","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1113\/expphysiol.2012.066613","article-title":"\u03b11-Adrenergic responsiveness in human skeletal muscle feed arteries: The impact of reducing extracellular pH","volume":"98","author":"Ives","year":"2013","journal-title":"Exp. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1161\/01.RES.71.1.201","article-title":"Effects of external pH on ionic currents in smooth muscle cells from the basilar artery of the guinea pig","volume":"71","author":"West","year":"1992","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1085\/jgp.103.4.665","article-title":"Calcium channel current of vascular smooth muscle cells: Extracellular protons modulate gating and single channel conductance","volume":"103","author":"Isenberg","year":"1994","journal-title":"J. Gen. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1097\/01.WCB.0000088764.02615.B7","article-title":"Cerebrovascular Vasodilation to Extraluminal Acidosis Occurs via Combined Activation of ATP-Sensitive and Ca2+-Activated Potassium Channels","volume":"23","author":"Lindauer","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ejphar.2011.01.053","article-title":"Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta","volume":"656","author":"Celotto","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000051027","article-title":"Protons inhibit the BKCa channel of rat small artery smooth muscle cells","volume":"38","author":"Schubert","year":"2001","journal-title":"J. Vasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/CIRCRESAHA.111.258145","article-title":"Acidosis dilates brain parenchymal arterioles by conversion of calcium waves to sparks to activate BK channels","volume":"110","author":"Dabertrand","year":"2012","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1161\/CIRCULATIONAHA.110.015974","article-title":"Disruption of NA+,HCO3- cotransporter NBCn1 (slc4a7) Inhibits no-mediated vasorelaxation, smooth muscle Ca2+ Sensitivity, and hypertension development in mice","volume":"124","author":"Boedtkjer","year":"2011","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/apha.12649","article-title":"EDH: Endothelium-dependent hyperpolarization and microvascular signalling","volume":"219","author":"Garland","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2018.03.004","article-title":"Acidosis potentiates endothelium-dependent vasorelaxation and gap junction communication in the superior mesenteric artery","volume":"827","author":"Mohanty","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gaynullina, D.K., Schubert, R., and Tarasova, O.S. (2019). Changes in endothelial nitric oxide production in systemic vessels during early ontogenesis\u2014A key mechanism for the perinatal adaptation of the circulatory system. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061421"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1161\/CIRCRESAHA.116.306531","article-title":"Thirty years of saying NO: Sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator","volume":"119","author":"Vanhoutte","year":"2016","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"805149","DOI":"10.3389\/fphys.2022.805149","article-title":"Endothelial Ion Channels and Cell-Cell Communication in the Microcirculation","volume":"13","author":"Jackson","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s00424-016-1839-0","article-title":"The eNOS signalosome and its link to endothelial dysfunction","volume":"468","author":"Siragusa","year":"2016","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/bph.14522","article-title":"Endothelial NOS: Perspective and recent developments","volume":"176","author":"Garcia","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.niox.2015.05.003","article-title":"Compartmentalized nitric oxide signaling in the resistance vasculature","volume":"49","author":"Mutchler","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.2174\/13816128113196660752","article-title":"Regulation of Endothelial Nitric Oxide Synthase Activity by Protein-Protein Interaction","volume":"20","author":"Su","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00424-009-0767-7","article-title":"Molecular mechanisms underlying the activation of eNOS","volume":"459","author":"Fleming","year":"2010","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1172\/JCI87343","article-title":"Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release","volume":"126","author":"Wang","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/cvr\/cvr104","article-title":"Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1","volume":"91","author":"Ching","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1111\/bph.15755","article-title":"Endothelial TRPV4\u2013eNOS coupling as a vital therapy target for treatment of hypertension","volume":"179","author":"Mao","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"H1699","DOI":"10.1152\/ajpheart.00493.2020","article-title":"Capillaries communicate with the arteriolar microvascular network by a pannexin\/purinergic-dependent pathway in hamster skeletal muscle","volume":"320","author":"Lamb","year":"2021","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fphys.2013.00347","article-title":"Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium","volume":"4","author":"Qian","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Sessa","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/21224","article-title":"Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation","volume":"399","author":"Dimmeler","year":"1999","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1161\/hh1101.092677","article-title":"Phosphorylation of Thr495 regulates Ca2+\/calmodulin-dependent endothelial nitric oxide synthase activity","volume":"88","author":"Fleming","year":"2001","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.atherosclerosis.2006.01.022","article-title":"Activation of endothelial nitric oxide synthase by cilostazol via a cAMP\/protein kinase A- and phosphatidylinositol 3-kinase\/Akt-dependent mechanism","volume":"189","author":"Hashimoto","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1074\/jbc.275.7.5179","article-title":"Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases","volume":"275","author":"Butt","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e145734","DOI":"10.1172\/JCI145734","article-title":"Protein kinase N2 mediates flow-induced endothelial NOS activation and vascular tone regulation","volume":"131","author":"Jin","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31629","DOI":"10.1074\/jbc.M212831200","article-title":"Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells","volume":"278","author":"Morrow","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1161\/01.ATV.0000221230.08596.98","article-title":"AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress","volume":"26","author":"Zhang","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"805","DOI":"10.2119\/molmed.2011.00461","article-title":"Implication of AMP-activated protein kinase in transient receptor potential vanilloid type 1-mediated activation of endothelial nitric oxide synthase","volume":"18","author":"Ching","year":"2012","journal-title":"Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1002\/jcp.23052","article-title":"AMP-activated protein kinase mediates erythropoietin-induced activation of endothelial nitric oxide synthase","volume":"227","author":"Su","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"42344","DOI":"10.1074\/jbc.M205144200","article-title":"Identification of regulatory sites of phosphorylation of the bovine endothelial nitric-oxide synthase at Serine 617 and Serine 635","volume":"277","author":"Michell","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101625","DOI":"10.1016\/j.redox.2020.101625","article-title":"Specific O-GlcNAc modification at Ser-615 modulates eNOS function","volume":"36","author":"Aulak","year":"2020","journal-title":"Redox Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14841","DOI":"10.1074\/jbc.M211926200","article-title":"Compensatory Phosphorylation and Protein-Protein Interactions Revealed by Loss of Function and Gain of Function Mutants of Multiple Serine Phosphorylation Sites in Endothelial Nitric-oxide Synthase","volume":"278","author":"Bauer","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"19888","DOI":"10.1074\/jbc.M413058200","article-title":"Receptor-regulated Dynamic S-Nitrosylation of Endothelial Nitric-oxide Synthase in Vascular Endothelial Cells","volume":"280","author":"Erwin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/1567202617999200819142021","article-title":"Propofol Protects Against TNF-\u03b1-induced Blood-brain Barrier Disruption via the PIM-1\/eNOS\/NO Pathway","volume":"17","author":"Lu","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1042\/BJ20060371","article-title":"Inhibition of MEK\/ERK1\/2 signalling alters endothelial nitric oxide synthase activity in an agonist-dependent manner","volume":"398","author":"Cale","year":"2006","journal-title":"Biochem. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/1440-1681.12136","article-title":"Endothelial caveolar subcellular domain regulation of endothelial nitric oxide synthase","volume":"40","author":"Ramadoss","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.bbrc.2007.07.030","article-title":"Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells","volume":"361","author":"Sugimoto","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"35943","DOI":"10.1074\/jbc.M504606200","article-title":"Src Kinase Activates Endothelial Nitric-oxide Synthase by Phosphorylating Tyr-83","volume":"280","author":"Fulton","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1093\/cvr\/cvaa213","article-title":"VE-PTP inhibition elicits eNOS phosphorylation to blunt endothelial dysfunction and hypertension in diabetes","volume":"117","author":"Siragusa","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1084\/jem.20090449","article-title":"Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase","volume":"206","author":"Loot","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1161\/CIRCRESAHA.108.172072","article-title":"Inhibition of Endothelial Nitric Oxide Synthase activity by Proline-Rich Tyrosine Kinase 2 in response to fluid shear stress and insulin","volume":"102","author":"Fisslthaler","year":"2008","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Daiber, A., Xia, N., Steven, S., Oelze, M., Hanf, A., Kr\u00f6ller-Sch\u00f6n, S., M\u00fcnzel, T., and Li, H. (2019). New therapeutic implications of endothelial nitric oxide synthase (eNOS) function\/dysfunction in cardiovascular disease. Int. J. Mol. Sci., 20, ISBN 6131176280.","DOI":"10.3390\/ijms20010187"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1182\/blood-2006-01-0141","article-title":"Vascular endothelial cell\u2013specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development","volume":"107","author":"Keller","year":"2006","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s12079-021-00611-9","article-title":"The role of vascular endothelial protein tyrosine phosphatase on nitric oxide synthase function in diabetes: From molecular biology to the clinic","volume":"15","author":"Justo","year":"2021","journal-title":"J. Cell Commun. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e007808","DOI":"10.1161\/JAHA.117.007808","article-title":"The unexpected role of calcium-activated potassium channels: Limitation of no-induced arterial relaxation","volume":"7","author":"Schmid","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gagov, H., Gribkova, I., Serebryakov, V., and Schubert, R. (2022). Sodium Nitroprusside-Induced Activation of Vascular Smooth Muscle BK Channels Is Mediated by PKG Rather Than by a Direct Interaction with NO. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052798"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1096\/fj.12-223669","article-title":"Specific phosphorylation sites underlie the stimulation of a large conductance, Ca2+-activated K+ channel by cGMP-dependent protein kinase","volume":"27","author":"Kyle","year":"2013","journal-title":"FASEB J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/cphy.c160011","article-title":"Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles","volume":"7","author":"Tykocki","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"H672","DOI":"10.1152\/ajpheart.00198.2011","article-title":"IRAG and novel PKG targeting in the cardiovascular system","volume":"301","author":"Schlossmann","year":"2011","journal-title":"Am. J. Physiol.-Hear. Circ. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1161\/CIRCRESAHA.107.153981","article-title":"cGMP-dependent relaxation of smooth muscle is coupled with the change in the phosphorylation of myosin phosphatase","volume":"101","author":"Nakamura","year":"2007","journal-title":"Circ. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Capellini, V.K., Restini, C.B.A., Bendhack, L.M., Evora, P.R.B., and Celotto, A.C. (2013). The Effect of Extracellular pH Changes on Intracellular pH and Nitric Oxide Concentration in Endothelial and Smooth Muscle Cells from Rat Aorta. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062887"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/S0024-3205(02)01914-8","article-title":"Augmentation of NO-mediated vasodilation in metabolic acidosis","volume":"71","author":"Hattori","year":"2002","journal-title":"Life Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e5007","DOI":"10.1590\/1414-431x20155007","article-title":"Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: An endothelium-dependent effect","volume":"49","author":"Celotto","year":"2016","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/cvr\/cvm014","article-title":"Coronary flow regulation in mouse heart during hypercapnic acidosis: Role of NO and its compensation during eNOS impairment","volume":"77","author":"Heintz","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_78","first-page":"H39","article-title":"Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis","volume":"268","author":"Gurevicius","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/jcbfm.1992.131","article-title":"Effect of nitric oxide blockade by NG-nitro-l-arginine on cerebral blood flow response to changes in carbon dioxide tension","volume":"12","author":"Wang","year":"1992","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/jcbfm.1993.70","article-title":"Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis","volume":"13","author":"Niwa","year":"1993","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1748-1716.1994.tb09821.x","article-title":"Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production","volume":"152","author":"You","year":"1994","journal-title":"Acta Physiol. Scand."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1097\/00004647-199609000-00032","article-title":"Hypercapnia relaxes cerebral arteries and potentiates neurally-induced relaxation","volume":"16","author":"Toda","year":"1996","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"R2005","DOI":"10.1152\/ajpregu.1997.273.6.R2005","article-title":"Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans","volume":"273","author":"Schmetterer","year":"1997","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1161\/01.RES.87.12.1149","article-title":"Prolonged hypercapnia-evoked cerebral hyperemia via K+ channel- and prostaglandin E2-dependent endothelial nitric oxide synthase induction","volume":"87","author":"Najarian","year":"2000","journal-title":"Circ. Res."},{"key":"ref_85","first-page":"1558","article-title":"PGE2-Mediated eNOS Induction in Prolonged Hypercapnia","volume":"43","author":"Checchin","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1097\/01.CCM.0000065678.24064.58","article-title":"Intravascular infusion of acid promotes intrapulmonary inducible nitric oxide synthase activity and impairs blood oxygenation in rats","volume":"31","author":"Haque","year":"2003","journal-title":"Crit. Care Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1152\/ajplung.00436.2001","article-title":"Alkalosis stimulates endothelial nitric oxide synthase in cultured human pulmonary arterial endothelial cells","volume":"283","author":"Mizuno","year":"2002","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"21420","DOI":"10.1074\/jbc.272.34.21420","article-title":"Decreased nitric-oxide synthase activity causes impaired endothelium- dependent relaxation in the postischemic heart","volume":"272","author":"Giraldez","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"H1424","DOI":"10.1152\/ajpheart.1993.265.4.H1424","article-title":"Modulation of calcium homeostasis in cultured rat aortic endothelial cells by intracellular acidification","volume":"265","author":"Ziegelstein","year":"1993","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1152\/jappl.2001.90.6.2094","article-title":"Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells","volume":"90","author":"Nishio","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.vph.2012.11.004","article-title":"Na +\/H + exchanger inhibitor induces vasorelaxation through nitric oxide production in endothelial cells via intracellular acidification-associated Ca2+ mobilization","volume":"58","author":"Sasahara","year":"2013","journal-title":"Vascul. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1161\/01.ATV.0000225698.36212.6a","article-title":"Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation","volume":"26","author":"Heyken","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"H466","DOI":"10.1152\/ajpheart.00854.2009","article-title":"TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress","volume":"298","author":"Mendoza","year":"2010","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"22664","DOI":"10.1074\/jbc.M302561200","article-title":"Impaired pressure sensation in mice lacking TRPV4","volume":"278","author":"Suzuki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_95","first-page":"692217","article-title":"GPR68 Contributes to Persistent Acidosis-Induced Activation of AGC Kinases and Tyrosine Phosphorylation in Organotypic Hippocampal Slices","volume":"1","author":"Wang","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"126083","DOI":"10.1155\/2013\/126083","article-title":"Transient acidosis during early reperfusion attenuates myocardium ischemia reperfusion injury VIA PI3K-AKT-enos signaling pathway","volume":"2013","author":"Qiao","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.gassur.2003.09.005","article-title":"Metabolic acidosis stimulates intestinal Glutamine absorption","volume":"7","author":"Epler","year":"2003","journal-title":"J. Gastrointest. Surg."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1681\/ASN.V441079","article-title":"Role of protein kinase C in the adaptive increase in Na-H antiporter in respiratory acidosis","volume":"4","author":"Pahlavan","year":"1993","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e13044","DOI":"10.1111\/apha.13044","article-title":"Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity","volume":"223","author":"Mochalov","year":"2018","journal-title":"Acta Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1007\/s00467-007-0561-8","article-title":"Blood pressure in the first year of life in healthy infants born at term","volume":"22","author":"Kent","year":"2007","journal-title":"Pediatr. Nephrol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000241004","article-title":"Postnatal development of cardiac output distribution measured by radioactive microspheres in rats","volume":"32","author":"Stulcova","year":"1977","journal-title":"Neonatology"},{"key":"ref_102","first-page":"377","article-title":"Age-dependent changes in the postnatal intestinal microcirculation","volume":"8","author":"Nankervis","year":"2001","journal-title":"Microcirculation"},{"key":"ref_103","first-page":"949","article-title":"Role of nitric oxide in regulation of vascular resistance in postnatal intestine","volume":"268","author":"Nankervis","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2016.02.005","article-title":"Endothelial nitric oxide weakens arterial contractile responses and reduces blood pressure during early postnatal development in rats","volume":"55\u201356","author":"Sofronova","year":"2016","journal-title":"Nitric Oxide-Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/cvr\/cvt138","article-title":"Functional remodelling of arterial endothelium during early postnatal development in rats","volume":"99","author":"Gaynullina","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"G1328","DOI":"10.1152\/ajpgi.00067.2002","article-title":"Developmental expression of eNOS in postnatal swine mesenteric artery","volume":"283","author":"Reber","year":"2002","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"H1168","DOI":"10.1152\/ajpheart.00029.2003","article-title":"Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs","volume":"285","author":"Chatrath","year":"2003","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Remzs\u0151, G., N\u00e9meth, J., Varga, V., Kov\u00e1cs, V., T\u00f3th-Sz\u0171ki, V., Kaila, K., Voipio, J., and Domoki, F. (2020). Brain interstitial pH changes in the subacute phase of hypoxic-ischemic encephalopathy in newborn pigs. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240643"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e03793","DOI":"10.1016\/j.heliyon.2020.e03793","article-title":"Prevalence of perinatal asphyxia in East and Central Africa: Systematic review and meta-analysis","volume":"6","author":"Workineh","year":"2017","journal-title":"Heliyon"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1478-4505-5-4","article-title":"Reducing one million child deaths from birth asphyxia-a survey of health systems gaps and priorities","volume":"5","author":"Lawn","year":"2007","journal-title":"Health Res. Policy Syst."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3389\/fped.2019.00489","article-title":"A Global View of Neonatal Asphyxia and Resuscitation","volume":"7","author":"Moshiro","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF02766785","article-title":"Effect of acidosis on contraction, intracellular pH, and calcium in the newborn and adult rabbit aorta","volume":"12","author":"Nakanishi","year":"1997","journal-title":"Heart Vessels"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1203\/00006450-199712000-00006","article-title":"Developmental changes in the effect of acidosis on contraction, intracellular pH, and calcium in the rabbit mesenteric small artery","volume":"42","author":"Nakanishi","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1152\/ajpregu.00222.2005","article-title":"Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes","volume":"289","author":"Reddy","year":"2005","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1523\/JNEUROSCI.3922-16.2017","article-title":"Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia","volume":"37","author":"Wenker","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_116","first-page":"121","article-title":"Development of adrenergic innervation in rat peripheral vessels: A fluorescence microscopic study","volume":"131","author":"Todd","year":"1980","journal-title":"J. Anat."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/apha.12331","article-title":"Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+ sensitivity during early post-natal development in rats","volume":"212","author":"Puzdrova","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/01.RES.41.1.19","article-title":"Contractile Properties of Small Arterial Resistance Vessels in Spontaneously Hypertensive and Normotensive Rats","volume":"41","author":"Mulvany","year":"1977","journal-title":"Circ. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/5987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:19:10Z","timestamp":1760138350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/5987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":118,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23115987"],"URL":"https:\/\/doi.org\/10.3390\/ijms23115987","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]}}}