{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:37:14Z","timestamp":1786703834127,"version":"build-2736575974"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"DFG","doi-asserted-by":"publisher","award":["SFB TRR259"],"award-info":[{"award-number":["SFB TRR259"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Carbon dioxide (CO2) can regulate blood flow and is applied therapeutically in intensive care units to treat brain injury, as well as in balneotherapy for peripheral arterial disease (PAD) and diabetic angiopathy; however, its mode of action remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The vasoactive CO2 effects were tested in arteries of healthy C57BL\/6J mice, hypertensive apolipoprotein E-deficient mice, and soluble guanylyl cyclase (sGC) knockout mice in a small vessel myograph with and without pharmacologically intervening in endothelium- and\/or vascular smooth muscle-mediated vasodilation. CO2-based near-infrared spectroscopy (NIRS-CO2) was developed to assess vasoreactivity of the skin microcirculation to CO2 in healthy individuals, PAD and coronary artery disease (CAD) patients, and was compared with flow-mediated dilation (FMD). We identified CO2 as a triple vasodilator mimicking the actions of endothelium-derived relaxing factor (nitric oxide, NO), endothelium-derived hyperpolarization factor, and direct myogenic vasodilators. CO2 engaged endothelial NO\/sGC, endothelial small-\/intermediate-conductance calcium-activated potassium channels (SKCa\/IKCa), and myogenic voltage-gated (KV) and IKCa potassium channels, respectively, acting as a triple vasodilator. CO2-evoked vasodilator responses were blunted and delayed in diseased human and murine arteries. In the human cohort, the NIRS-CO2-derived time-to-intersection of the HbO2 and HHb curves, capturing the delay phenotype, showed a strong association with PAD\/CAD status and, in exploratory analyses, also distinguished young individuals with cardiovascular risk factors, supporting NIRS-CO2 as a physiological readout that integrates endothelial and myogenic components of microvascular reactivity. Duration and extent of CO2 vasodilation were coupled to tissue metabolism through vascular carbonic anhydrases (CAs), providing a mechanism for vasculometabolic coupling and one for clinically approved CA inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NIRS-CO2 provides a feasible readout of CO2-evoked microvascular responsiveness and shows disease-associated alterations in our PAD\/CAD cohort. Larger studies will validate generalizability across vasculopathies and clarify the relative contributions of NO-sGC vs. K+ channel-linked mechanisms for future therapeutic translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag134","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:41:29Z","timestamp":1781955689000},"page":"1530-1541","source":"Crossref","is-referenced-by-count":0,"title":["Carbon dioxide is a triple vasodilator"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-1016","authenticated-orcid":false,"given":"Dragos A","family":"Duse","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine III, University Hospital D\u00fcsseldorf, Heinrich Heine University , Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie H","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine III, University Hospital D\u00fcsseldorf, Heinrich Heine University , Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Akritidis","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of General, Visceral, Vascular and Transplantation Surgery, University of Duisburg-Essen, Hufelandstra\u00dfe 55 , 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"K\u00e4lsch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothe","family":"M\u00f6llmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlattjan","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine III, University Hospital D\u00fcsseldorf, Heinrich Heine University , Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evanthia","family":"Mergia","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Ruhr-University Bochum , Universit\u00e4tsstrasse 150, 44780 Bochum ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lainka","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of General, Visceral, Vascular and Transplantation Surgery, University of Duisburg-Essen, Hufelandstra\u00dfe 55 , 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt W","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph M","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Wichmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Polzin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"CARID - Cardiovascular Research Institute D\u00fcsseldorf , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Erkens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8325-250X","authenticated-orcid":false,"given":"Christian","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"CARID - Cardiovascular Research Institute D\u00fcsseldorf , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-1052","authenticated-orcid":false,"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"CARID - Cardiovascular Research Institute D\u00fcsseldorf , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-125X","authenticated-orcid":false,"given":"Bodo","family":"Levkau","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine III, University Hospital D\u00fcsseldorf, Heinrich Heine University , Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"CARID - Cardiovascular Research Institute D\u00fcsseldorf , Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-5318","authenticated-orcid":false,"given":"Hideo A","family":"Baba","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"2026081406121087800_cvag134-B1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1089\/ars.2016.6909","article-title":"Gasotransmitter heterocellular signaling","volume":"26","author":"Kolluru","year":"2017","journal-title":"Antioxid Redox Signal"},{"key":"2026081406121087800_cvag134-B2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1152\/ajplegacy.1935.111.3.557","article-title":"Changes in human cerebral blood flow consequent on alterations in blood gases","volume":"111","author":"Gibbs","year":"1935","journal-title":"Am J Physiol"},{"key":"2026081406121087800_cvag134-B3","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1097\/00000542-199805000-00029","article-title":"Carbon dioxide and the cerebral circulation","volume":"88","author":"Brian Johnny","year":"1998","journal-title":"Anesthesiology"},{"key":"2026081406121087800_cvag134-B4","doi-asserted-by":"crossref","first-page":"H1856","DOI":"10.1152\/ajpheart.00014.2006","article-title":"Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction","volume":"291","author":"Lavi","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026081406121087800_cvag134-B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00408-010-9234-7","article-title":"Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1","volume":"188","author":"Chuang","year":"2010","journal-title":"Lung"},{"key":"2026081406121087800_cvag134-B6","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1161\/01.STR.25.8.1679","article-title":"Cerebral vasodilation during hypercapnia. Role of glibenclamide-sensitive potassium channels and nitric oxide","volume":"25","author":"Faraci","year":"1994","journal-title":"Stroke"},{"key":"2026081406121087800_cvag134-B7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainres.2011.02.066","article-title":"Carbon dioxide influence on nitric oxide production in endothelial cells and astrocytes: cellular mechanisms","volume":"1386","author":"Fathi","year":"2011","journal-title":"Brain Res"},{"key":"2026081406121087800_cvag134-B8","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.3390\/ijms20153841","article-title":"Role of carbonic anhydrases and inhibitors in acid-base physiology: insights from mathematical modeling","volume":"20","author":"Occhipinti","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026081406121087800_cvag134-B9","doi-asserted-by":"crossref","first-page":"1338528","DOI":"10.3389\/fmolb.2024.1338528","article-title":"Carbonic anhydrase, its inhibitors and vascular function","volume":"11","author":"Garc\u00eda-Llorca","year":"2024","journal-title":"Front Mol Biosci"},{"key":"2026081406121087800_cvag134-B10","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/CRD.0b013e31822b4939","article-title":"Acetazolamide: a forgotten diuretic agent","volume":"19","author":"Kassamali","year":"2011","journal-title":"Cardiol Rev"},{"key":"2026081406121087800_cvag134-B11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.artres.2016.09.001","article-title":"Recent developments in near-infrared spectroscopy (NIRS) for the assessment of local skeletal muscle microvascular function and capacity to utilise oxygen","volume":"16","author":"Jones","year":"2016","journal-title":"Artery Res"},{"key":"2026081406121087800_cvag134-B12","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1161\/01.STR.26.12.2285","article-title":"Can cerebrovascular reactivity be measured with near-infrared spectroscopy?","volume":"26","author":"Smielewski","year":"1995","journal-title":"Stroke"},{"key":"2026081406121087800_cvag134-B13","article-title":"Subcutaneous angiotensin II infusion using osmotic pumps induces aortic aneurysms in mice","volume":"2015","author":"Lu","year":"2015","journal-title":"J Vis Exp"},{"key":"2026081406121087800_cvag134-B14","doi-asserted-by":"crossref","first-page":"7562","DOI":"10.1039\/D3FO01737K","article-title":"Cocoa flavanols improve peak VO(2) and exercise capacity in a randomized double blinded clinical trial in healthy elderly people","volume":"14","author":"Gr\u00f6ne","year":"2023","journal-title":"Food Funct"},{"key":"2026081406121087800_cvag134-B15","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1111\/bph.16483","article-title":"Inhibition of proline-rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes","volume":"181","author":"Erkens","year":"2024","journal-title":"Br J Pharmacol"},{"key":"2026081406121087800_cvag134-B16","doi-asserted-by":"crossref","first-page":"115041","DOI":"10.1016\/j.bcp.2022.115041","article-title":"Carbon monoxide signaling and soluble guanylyl cyclase: facts, myths, and intriguing possibilities","volume":"200","author":"Lu","year":"2022","journal-title":"Biochem Pharmacol"},{"key":"2026081406121087800_cvag134-B17","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1172\/JCI27657","article-title":"Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system","volume":"116","author":"Mergia","year":"2006","journal-title":"J Clin Invest"},{"key":"2026081406121087800_cvag134-B18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/j.2040-4603.2017.tb00747.x","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":"2026081406121087800_cvag134-B19","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1021\/bi00144a011","article-title":"Mechanism of iberiotoxin block of the large-conductance calcium-activated potassium channel from bovine aortic smooth muscle","volume":"31","author":"Giangiacomo","year":"1992","journal-title":"Biochemistry"},{"key":"2026081406121087800_cvag134-B20","doi-asserted-by":"crossref","first-page":"C799","DOI":"10.1152\/ajpcell.1995.268.4.C799","article-title":"Physiological roles and properties of potassium channels in arterial smooth muscle","volume":"268","author":"Nelson","year":"1995","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026081406121087800_cvag134-B21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0063028","article-title":"TRAM-34, a putatively selective blocker of intermediate-conductance, calcium-activated potassium channels, inhibits cytochrome P450 activity","volume":"8","author":"Agarwal","year":"2013","journal-title":"PLoS One"},{"key":"2026081406121087800_cvag134-B22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/BF00584654","article-title":"Features of 4-aminopyridine sensitive outward current observed in single smooth muscle cells from the rabbit pulmonary artery","volume":"409","author":"Okabe","year":"1987","journal-title":"Pflugers Arch"},{"key":"2026081406121087800_cvag134-B23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1152\/physiol.00040.2005","article-title":"Calcium-activated potassium channels and the regulation of vascular tone","volume":"21","author":"Ledoux","year":"2006","journal-title":"Physiology"},{"key":"2026081406121087800_cvag134-B24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/24388","article-title":"K+ is an endothelium-derived hyperpolarizing factor in rat arteries","volume":"396","author":"Edwards","year":"1998","journal-title":"Nature"},{"key":"2026081406121087800_cvag134-B25","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/j.1476-5381.2010.01148.x","article-title":"EDHF: spreading the influence of the endothelium","volume":"164","author":"Garland","year":"2011","journal-title":"Br J Pharmacol"},{"key":"2026081406121087800_cvag134-B26","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0140-6736(92)93147-F","article-title":"Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis","volume":"340","author":"Celermajer","year":"1992","journal-title":"Lancet (London, England)"},{"key":"2026081406121087800_cvag134-B27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1177\/000331979704800406","article-title":"Effect of carbon dioxide-enriched water and fresh water on the cutaneous microcirculation and oxygen tension in the skin of the foot","volume":"48","author":"Hartmann","year":"1997","journal-title":"Angiology"},{"key":"2026081406121087800_cvag134-B28","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fphys.2012.00365","article-title":"pCO(2) and pH regulation of cerebral blood flow","volume":"3","author":"Yoon","year":"2012","journal-title":"Front Physiol"},{"key":"2026081406121087800_cvag134-B29","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":"2026081406121087800_cvag134-B30","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":"2026081406121087800_cvag134-B31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00424-010-0916-z","article-title":"CO2-dependent opening of an inwardly rectifying K+ channel","volume":"461","author":"Huckstepp","year":"2011","journal-title":"Pflugers Arch"},{"key":"2026081406121087800_cvag134-B32","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1161\/01.STR.30.4.851","article-title":"Blockade of ATP-sensitive potassium channels in cerebral arterioles inhibits vasoconstriction from hypocapnic alkalosis in cats","volume":"30","author":"Wei","year":"1999","journal-title":"Stroke"},{"key":"2026081406121087800_cvag134-B33","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1161\/01.STR.26.9.1713","article-title":"Role of potassium channels in cerebral blood vessels","volume":"26","author":"Kitazono","year":"1995","journal-title":"Stroke"},{"key":"2026081406121087800_cvag134-B34","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/ki.2009.221","article-title":"Hydrogen sulfide: a new EDRF","volume":"76","author":"Wang","year":"2009","journal-title":"Kidney Int"},{"key":"2026081406121087800_cvag134-B35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1167\/iovs.08-2435","article-title":"The vasodilating effect of acetazolamide and dorzolamide involves mechanisms other than carbonic anhydrase inhibition","volume":"50","author":"Torring","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026081406121087800_cvag134-B36","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/sj.bjp.0703825","article-title":"In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature","volume":"132","author":"Pickkers","year":"2001","journal-title":"Br J Pharmacol"},{"key":"2026081406121087800_cvag134-B37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0305-0491(79)90119-6","article-title":"Comparative properties of mammalian and insect carbonic anhydrases: effects of potassium and chloride on the rate of carbon dioxide hydration","volume":"62","author":"Johnston","year":"1979","journal-title":"Comp Biochem Physiol B"},{"key":"2026081406121087800_cvag134-B38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF00373747","article-title":"Differential contractile effects of changes in carbon dioxide tension on rat mesenteric resistance arteries precontracted with noradrenaline","volume":"419","author":"Nielsen","year":"1991","journal-title":"Pflugers Arch"},{"key":"2026081406121087800_cvag134-B39","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/BF00582922","article-title":"Effect of H+ and elevated PCO2 on membrane electrical properties of rat cerebral arteries","volume":"394","author":"Harder","year":"1982","journal-title":"Pflugers Arch"},{"key":"2026081406121087800_cvag134-B40","doi-asserted-by":"crossref","first-page":"9183","DOI":"10.1074\/jbc.M114.625715","article-title":"High CO2 levels cause skeletal muscle atrophy via AMP-activated kinase (AMPK), FoxO3a protein, and muscle-specific ring finger protein 1 (MuRF1)","volume":"290","author":"Jaitovich","year":"2015","journal-title":"J Biol Chem"},{"key":"2026081406121087800_cvag134-B41","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1074\/jbc.M807239200","article-title":"Stimulation of mammalian G-protein-responsive adenylyl cyclases by carbon dioxide","volume":"284","author":"Townsend","year":"2009","journal-title":"J Biol Chem"},{"key":"2026081406121087800_cvag134-B42","doi-asserted-by":"crossref","DOI":"10.3389\/fpls.2022.994149","article-title":"Nitric oxide: a core signaling molecule under elevated GHGs (CO(2), CH(4), N(2)O, O(3))-mediated abiotic stress in plants","volume":"13","author":"Kabange","year":"2022","journal-title":"Front Plant Sci"},{"key":"2026081406121087800_cvag134-B43","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0735-1097(01)01746-6","article-title":"Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force","volume":"39","author":"Corretti","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2026081406121087800_cvag134-B44","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.3390\/jcm13071892","article-title":"Retinal vascular changes in heart failure with preserved ejection fraction using Optical Coherence Tomography Angiography","volume":"13","author":"Weerts","year":"2024","journal-title":"J Clin Med"},{"key":"2026081406121087800_cvag134-B45","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1161\/CIRCULATIONAHA.107.748574","article-title":"Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham heart study","volume":"117","author":"Hamburg","year":"2008","journal-title":"Circulation"},{"key":"2026081406121087800_cvag134-B46","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002270","article-title":"Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis","volume":"4","author":"Matsuzawa","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"2026081406121087800_cvag134-B47","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1161\/01.CIR.0000149748.79945.52","article-title":"Impaired l-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects","volume":"110","author":"Schlaich","year":"2004","journal-title":"Circulation"},{"key":"2026081406121087800_cvag134-B48","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1161\/CIRCULATIONAHA.110.981738","article-title":"Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease","volume":"123","author":"Stasch","year":"2011","journal-title":"Circulation"},{"key":"2026081406121087800_cvag134-B49","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1056\/NEJM199507273330403","article-title":"Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension","volume":"333","author":"Giaid","year":"1995","journal-title":"N Engl J Med"},{"key":"2026081406121087800_cvag134-B50","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1517\/14728220903540257","article-title":"Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease","volume":"14","author":"K\u00f6hler","year":"2010","journal-title":"Expert Opin Ther Targets"},{"key":"2026081406121087800_cvag134-B51","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1124\/mol.108.051425","article-title":"Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure","volume":"75","author":"Sankaranarayanan","year":"2009","journal-title":"Mol Pharmacol"},{"key":"2026081406121087800_cvag134-B52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1161\/01.RES.79.2.295","article-title":"Alterations in rat interlobar artery membrane potential and K+ channels in genetic and nongenetic hypertension","volume":"79","author":"Martens","year":"1996","journal-title":"Circ Res"},{"key":"2026081406121087800_cvag134-B53","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1161\/01.CIR.98.14.1400","article-title":"Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension","volume":"98","author":"Yuan","year":"1998","journal-title":"Circulation"},{"key":"2026081406121087800_cvag134-B54","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1161\/01.ATV.21.1.28","article-title":"Potassium channel function in vascular disease","volume":"21","author":"Sobey","year":"2001","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026081406121087800_cvag134-B55","doi-asserted-by":"crossref","first-page":"103988","DOI":"10.1016\/j.archger.2019.103988","article-title":"Age and sex differences in frontal lobe cerebral oxygenation in older adults-normative values using novel, scalable technology: findings from the Irish longitudinal study on ageing (TILDA)","volume":"87","author":"Newman","year":"2020","journal-title":"Arch Gerontol Geriatr"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvag134\/68583812\/cvag134.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvag134\/68583812\/cvag134.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvag134\/68583812\/cvag134.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:14:03Z","timestamp":1786702443000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/122\/11\/1530\/8713800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6,23]]},"published-print":{"date-parts":[[2026,8,14]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvag134","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,6,23]]}}}