{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:10:43Z","timestamp":1784229043794,"version":"3.55.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammation and vascular smooth muscle cell (VSMC) phenotypic switching are causally linked to pulmonary arterial hypertension (PAH) pathogenesis. Carbonic anhydrase inhibition induces mild metabolic acidosis and exerts protective effects in hypoxic pulmonary hypertension. Carbonic anhydrases and metabolic acidosis are further known to modulate immune cell activation. To evaluate if carbonic anhydrase inhibition modulates macrophage activation, inflammation, and VSMC phenotypic switching in severe experimental pulmonary hypertension, pulmonary hypertension was assessed in Sugen 5416\/hypoxia (SU\/Hx) rats after treatment with acetazolamide or ammonium chloride (NH4Cl). We evaluated pulmonary and systemic inflammation and characterized the effect of carbonic anhydrase inhibition and metabolic acidosis in alveolar macrophages and bone marrow\u2013derived macrophages (BMDMs). We further evaluated the treatment effects on VSMC phenotypic switching in pulmonary arteries and pulmonary artery smooth muscle cells (PASMCs) and corroborated some of our findings in lungs and pulmonary arteries of patients with PAH. Both patients with idiopathic PAH and SU\/Hx rats had increased expression of lung inflammatory markers and signs of PASMC dedifferentiation in pulmonary arteries. Acetazolamide and NH4Cl ameliorated SU\/Hx-induced pulmonary hypertension and blunted pulmonary and systemic inflammation. Expression of carbonic anhydrase isoform 2 was increased in alveolar macrophages from SU\/Hx animals, classically (M1) and alternatively (M2) activated BMDMs, and lungs of patients with PAH. Carbonic anhydrase inhibition and acidosis had distinct effects on M1 and M2 markers in BMDMs. Inflammatory cytokines drove PASMC dedifferentiation, and this was inhibited by acetazolamide and acidosis. The protective antiinflammatory effect of acetazolamide in pulmonary hypertension is mediated by a dual mechanism of macrophage carbonic anhydrase inhibition and systemic metabolic acidosis.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0232oc","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T17:05:53Z","timestamp":1554483953000},"page":"512-524","source":"Crossref","is-referenced-by-count":74,"title":["Carbonic Anhydrase Inhibition Ameliorates Inflammation and Experimental Pulmonary Hypertension"],"prefix":"10.1093","volume":"61","author":[{"given":"Hannes","family":"Hudalla","sequence":"first","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"},{"name":"Department of Neonatology, Heidelberg University Children\u2019s Hospital, Heidelberg, Germany"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Michael","sequence":"additional","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth R.","family":"Willis","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Fernandez-Gonzalez","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia J.","family":"Filatava","sequence":"additional","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Dieffenbach","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Fredenburgh","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Stearman","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care Medicine, Sleep, and Occupational Medicine, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Geraci","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care Medicine, Sleep, and Occupational Medicine, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Kourembanas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Christou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Newborn Medicine and"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2026021100403352100_bib1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1056\/NEJMra035488","article-title":"Pulmonary arterial hypertension","volume":"351","author":"Farber","year":"2004","journal-title":"N Engl J Med"},{"key":"2026021100403352100_bib2","doi-asserted-by":"crossref","first-page":"L229","DOI":"10.1152\/ajplung.00238.2014","article-title":"The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes","volume":"308","author":"Pugliese","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100403352100_bib3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/CIRCRESAHA.113.301141","article-title":"Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension","volume":"115","author":"Rabinovitch","year":"2014","journal-title":"Circ Res"},{"key":"2026021100403352100_bib4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1164\/rccm.201202-0335OC","article-title":"Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension","volume":"186","author":"Savai","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021100403352100_bib5","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCULATIONAHA.109.933762","article-title":"Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension","volume":"122","author":"Soon","year":"2010","journal-title":"Circulation"},{"key":"2026021100403352100_bib6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1164\/rccm.201201-0164OC","article-title":"Modern age pathology of pulmonary arterial hypertension","volume":"186","author":"Stacher","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021100403352100_bib7","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1161\/CIRCRESAHA.108.182014","article-title":"Interleukin-6 overexpression induces pulmonary hypertension","volume":"104","author":"Steiner","year":"2009","journal-title":"Circ Res"},{"key":"2026021100403352100_bib8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1465-9921-15-47","article-title":"Inflammatory cytokines in pulmonary hypertension","volume":"15","author":"Groth","year":"2014","journal-title":"Respir Res"},{"key":"2026021100403352100_bib9","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1161\/CIRCULATIONAHA.110.978627","article-title":"Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension","volume":"123","author":"Vergadi","year":"2011","journal-title":"Circulation"},{"key":"2026021100403352100_bib10","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1073\/pnas.161272598","article-title":"Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia","volume":"98","author":"Minamino","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021100403352100_bib11","doi-asserted-by":"crossref","first-page":"E2677","DOI":"10.1073\/pnas.1424774112","article-title":"Interleukin-6\/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension","volume":"112","author":"Hashimoto-Kataoka","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021100403352100_bib12","doi-asserted-by":"crossref","first-page":"14079","DOI":"10.1038\/ncomms14079","article-title":"TNF\u03b1 drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling","volume":"8","author":"Hurst","year":"2017","journal-title":"Nat Commun"},{"key":"2026021100403352100_bib13","doi-asserted-by":"crossref","first-page":"200ra117","DOI":"10.1126\/scitranslmed.3006674","article-title":"Blocking macrophage leukotriene B4 prevents endothelial injury and reverses pulmonary hypertension","volume":"5","author":"Tian","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026021100403352100_bib14","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1164\/rccm.201608-1630PP","article-title":"The roles of immunity in the prevention and evolution of pulmonary arterial hypertension","volume":"195","author":"Nicolls","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021100403352100_bib15","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2353\/ajpath.2006.050599","article-title":"Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte\/macrophage lineage","volume":"168","author":"Frid","year":"2006","journal-title":"Am J Pathol"},{"key":"2026021100403352100_bib16","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/ATVBAHA.114.305218","article-title":"Myocardin regulates vascular smooth muscle cell inflammatory activation and disease","volume":"35","author":"Ackers-Johnson","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026021100403352100_bib17","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1073\/pnas.0705842105","article-title":"Myocardin inhibits cellular proliferation by inhibiting NF-\u03baB(p65)-dependent cell cycle progression","volume":"105","author":"Tang","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021100403352100_bib18","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/nm.3695","article-title":"Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension","volume":"20","author":"Savai","year":"2014","journal-title":"Nat Med"},{"key":"2026021100403352100_bib19","doi-asserted-by":"crossref","first-page":"L875","DOI":"10.1152\/ajplung.00293.2011","article-title":"Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension","volume":"302","author":"Christou","year":"2012","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100403352100_bib20","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1084\/jem.20151739","article-title":"Carbonic anhydrase enzymes regulate mast cell-mediated inflammation","volume":"213","author":"Henry","year":"2016","journal-title":"J Exp Med"},{"key":"2026021100403352100_bib21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm.3804","article-title":"The ketone metabolite \u03b2-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease","volume":"21","author":"Youm","year":"2015","journal-title":"Nat Med"},{"key":"2026021100403352100_bib22","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1158\/0008-5472.CAN-15-1743","article-title":"Neutralization of tumor acidity improves antitumor responses to immunotherapy","volume":"76","author":"Pilon-Thomas","year":"2016","journal-title":"Cancer Res"},{"key":"2026021100403352100_bib23","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"2026021100403352100_bib24","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.4049\/jimmunol.0803466","article-title":"Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages","volume":"182","author":"Mogi","year":"2009","journal-title":"J Immunol"},{"key":"2026021100403352100_bib25","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"2026021100403352100_bib26","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1183\/09031936.00216011","article-title":"Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics","volume":"40","author":"Pichon","year":"2012","journal-title":"Eur Respir J"},{"key":"2026021100403352100_bib27","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1161\/CIRCULATIONAHA.109.927681","article-title":"Formation of plexiform lesions in experimental severe pulmonary arterial hypertension","volume":"121","author":"Abe","year":"2010","journal-title":"Circulation"},{"key":"2026021100403352100_bib28","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1214\/aos\/1074290335","article-title":"The positive false discovery rate: a Bayesian interpretation and the q-value","volume":"31","author":"Storey","year":"2003","journal-title":"Ann Stat"},{"key":"2026021100403352100_bib29","doi-asserted-by":"crossref","first-page":"e0118655","DOI":"10.1371\/journal.pone.0118655","article-title":"Potential contribution of phenotypically modulated smooth muscle cells and related inflammation in the development of experimental obstructive pulmonary vasculopathy in rats","volume":"10","author":"Otsuki","year":"2015","journal-title":"PLoS One"},{"key":"2026021100403352100_bib30","doi-asserted-by":"crossref","first-page":"597","DOI":"10.4049\/jimmunol.1303048","article-title":"Adventitial fibroblasts induce a distinct proinflammatory\/profibrotic macrophage phenotype in pulmonary hypertension","volume":"193","author":"El Kasmi","year":"2014","journal-title":"J Immunol"},{"key":"2026021100403352100_bib31","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1152\/japplphysiol.00312.2007","article-title":"Alveolar macrophages are necessary for the systemic inflammation of acute alveolar hypoxia","volume":"103","author":"Gonzalez","year":"2007","journal-title":"J Appl Physiol (1985)"},{"key":"2026021100403352100_bib32","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.4049\/jimmunol.1302846","article-title":"Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils","volume":"192","author":"Wen","year":"2014","journal-title":"J Immunol"},{"key":"2026021100403352100_bib33","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.smim.2015.09.001","article-title":"Contribution of metabolic reprogramming to macrophage plasticity and function","volume":"27","author":"El Kasmi","year":"2015","journal-title":"Semin Immunol"},{"key":"2026021100403352100_bib34","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/nm.2021","article-title":"Notch3 signaling promotes the development of pulmonary arterial hypertension","volume":"15","author":"Li","year":"2009","journal-title":"Nat Med"},{"key":"2026021100403352100_bib35","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1164\/rccm.201304-0700OC","article-title":"Endothelial indoleamine 2,3-dioxygenase protects against development of pulmonary hypertension","volume":"188","author":"Xiao","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021100403352100_bib36","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/jcbfm.2013.109","article-title":"TNF-\u03b1 induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology","volume":"33","author":"Ali","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026021100403352100_bib37","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1161\/ATVBAHA.113.303145","article-title":"Cross talk between vascular smooth muscle cells and monocytes through interleukin-1\u03b2\/interleukin-18 signaling promotes vein graft thickening","volume":"34","author":"Li","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026021100403352100_bib38","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000321555","article-title":"Heme oxygenase-1 does not mediate the effects of extracellular acidosis on vascular smooth muscle cell proliferation, migration, and susceptibility to apoptosis","volume":"48","author":"Brenninkmeijer","year":"2011","journal-title":"J Vasc Res"},{"key":"2026021100403352100_bib39","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/1471-2407-13-378","article-title":"Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines","volume":"13","author":"Mokhtari","year":"2013","journal-title":"BMC Cancer"},{"key":"2026021100403352100_bib40","doi-asserted-by":"crossref","first-page":"36085","DOI":"10.1074\/jbc.M111952200","article-title":"Carbonic anhydrase II binds to and enhances activity of the Na+\/H+ exchanger","volume":"277","author":"Li","year":"2002","journal-title":"J Biol Chem"},{"key":"2026021100403352100_bib41","doi-asserted-by":"crossref","first-page":"H228","DOI":"10.1152\/ajpheart.00055.2013","article-title":"Inhibition of carbonic anhydrase prevents the Na+\/H+ exchanger 1-dependent slow force response to rat myocardial stretch","volume":"305","author":"Vargas","year":"2013","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026021100403352100_bib42","doi-asserted-by":"crossref","first-page":"e12729","DOI":"10.14814\/phy2.12729","article-title":"The Na+\/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension","volume":"4","author":"Huetsch","year":"2016","journal-title":"Physiol Rep"},{"key":"2026021100403352100_bib43","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1164\/rccm.200710-1522OC","article-title":"Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling","volume":"177","author":"Yu","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021100403352100_bib44","doi-asserted-by":"crossref","first-page":"F678","DOI":"10.1152\/ajprenal.00097.2002","article-title":"p38 MAPK mediates acid-induced transcription of PEPCK in LLC-PK1-FBPase+ cells","volume":"283","author":"Feifel","year":"2002","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026021100403352100_bib45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1677\/jme.0.0270043","article-title":"Regulation of apoA1 gene expression with acidosis: requirement for a transcriptional repressor","volume":"27","author":"Haas","year":"2001","journal-title":"J Mol Endocrinol"},{"key":"2026021100403352100_bib46","doi-asserted-by":"crossref","first-page":"L1291","DOI":"10.1152\/ajplung.00246.2001","article-title":"Inhibition of apoptosis in pulmonary endothelial cells by altered pH, mitochondrial function, and ATP supply","volume":"283","author":"Terminella","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100403352100_bib47","doi-asserted-by":"crossref","first-page":"H917","DOI":"10.1152\/ajpheart.01067.2001","article-title":"Hypoxia and acidosis impair cGMP synthesis in microvascular coronary endothelial cells","volume":"283","author":"Agull\u00f3","year":"2002","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026021100403352100_bib48","doi-asserted-by":"crossref","first-page":"9804","DOI":"10.1074\/jbc.273.16.9804","article-title":"Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart","volume":"273","author":"Vittone","year":"1998","journal-title":"J Biol Chem"},{"key":"2026021100403352100_bib49","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1161\/01.RES.78.1.50","article-title":"Acidosis-induced coronary arteriolar dilation is mediated by ATP-sensitive potassium channels in vascular smooth muscle","volume":"78","author":"Ishizaka","year":"1996","journal-title":"Circ Res"},{"key":"2026021100403352100_bib50","first-page":"H1351","article-title":"Intracellular acidosis differentially regulates KV channels in coronary and pulmonary vascular muscle","volume":"275","author":"Berger","year":"1998","journal-title":"Am J Physiol"},{"key":"2026021100403352100_bib51","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1161\/01.RES.86.3.355","article-title":"Interactions between Ca2+ and H+ and functional consequences in vascular smooth muscle","volume":"86","author":"Austin","year":"2000","journal-title":"Circ Res"},{"key":"2026021100403352100_bib52","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1161\/CIRCRESAHA.110.236927","article-title":"Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension","volume":"109","author":"Tamosiuniene","year":"2011","journal-title":"Circ Res"},{"key":"2026021100403352100_bib53","first-page":"CD009761","article-title":"Interventions for preventing high altitude illness: part 1. Commonly-used classes of drugs","volume":"6","author":"Nieto Estrada","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"2026021100403352100_bib54","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.5665\/sleep.6080","article-title":"Patients with obstructive sleep apnea have cardiac repolarization disturbances when travelling to altitude: randomized, placebo-controlled trial of acetazolamide","volume":"39","author":"Latshang","year":"2016","journal-title":"Sleep (Basel)"},{"key":"2026021100403352100_bib55","doi-asserted-by":"crossref","first-page":"L1002","DOI":"10.1152\/ajplung.00161.2006","article-title":"Inhibition of hypoxia-induced calcium responses in pulmonary arterial smooth muscle by acetazolamide is independent of carbonic anhydrase inhibition","volume":"292","author":"Shimoda","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100403352100_bib56","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1183\/09031936.98.12061242","article-title":"Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression","volume":"12","author":"Swenson","year":"1998","journal-title":"Eur Respir J"},{"key":"2026021100403352100_bib57","doi-asserted-by":"crossref","first-page":"H2068","DOI":"10.1152\/ajpheart.00525.2009","article-title":"Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation","volume":"297","author":"Aamand","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026021100403352100_bib58","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature14620","article-title":"The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia","volume":"524","author":"Zhao","year":"2015","journal-title":"Nature"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/61\/4\/512\/66762971\/ajrcmb_61_4_512.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/61\/4\/512\/66762971\/ajrcmb_61_4_512.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:40:44Z","timestamp":1770788444000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/61\/4\/512\/8461479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,10,1]]},"published-print":{"date-parts":[[2019,10,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2018-0232oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,10,1]]}}}