{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:56Z","timestamp":1787028416623,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wan Fang Hospital, Taiwan","award":["107-wf-eva-21"],"award-info":[{"award-number":["107-wf-eva-21"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2314-B-303-001-MY3 and MOST-105-2811-B-303-005"],"award-info":[{"award-number":["MOST 105-2314-B-303-001-MY3 and MOST-105-2811-B-303-005"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg\/kg). MgSO4 (100 mg\/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, \u03b1-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p &lt; 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p &lt; 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.<\/jats:p>","DOI":"10.3390\/ijms20184622","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:01:15Z","timestamp":1568804475000},"page":"4622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats"],"prefix":"10.3390","volume":"20","author":[{"given":"Chao-Yuan","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Jen","family":"Shih","sequence":"additional","affiliation":[{"name":"Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Education Unit, Redcliffe Hospital, Metro North Hospital and Health Service, Queensland Government, Redcliffe, QLD 4020, Australia"},{"name":"School of Public Health, Faculty of Medicine, University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Shan","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Nursing, College of Nursing, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kung-Yen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1006-6762","authenticated-orcid":false,"given":"Chun-Jen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"ref_1","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":"ref_2","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1161\/CIRCULATIONAHA.104.503540","article-title":"Pulmonary arterial hypertension","volume":"114","author":"McLaughlin","year":"2006","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1378\/chest.14-0793","article-title":"Pharmacologic therapy for pulmonary arterial hypertension in adults: Chest guideline and expert panel report","volume":"146","author":"Taichman","year":"2014","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"j5492","DOI":"10.1136\/bmj.j5492","article-title":"Pulmonary arterial hypertension: Pathogenesis and clinical management","volume":"360","author":"Thenappan","year":"2018","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1700740","DOI":"10.1183\/13993003.00740-2017","article-title":"Mortality in pulmonary arterial hypertension: Prediction by the 2015 european pulmonary hypertension guidelines risk stratification model","volume":"50","author":"Hoeper","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00441-016-2539-y","article-title":"Pulmonary vascular remodeling in pulmonary hypertension","volume":"367","author":"Tuder","year":"2017","journal-title":"Cell. Tissue. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2119\/molmed.2013.00165","article-title":"Molecular mechanisms of pulmonary arterial remodeling","volume":"20","author":"Crosswhite","year":"2014","journal-title":"Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00109-010-0670-x","article-title":"The role of mitochondria in pulmonary vascular remodeling","volume":"8","author":"Dromparis","year":"2010","journal-title":"J. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1172\/JCI23203","article-title":"Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension","volume":"115","author":"McMurtry","year":"2005","journal-title":"J. Clin. Invest."},{"key":"ref_10","first-page":"394","article-title":"A meta-analysis of randomized controlled trials in pulmonary arterial hypertension","volume":"30","author":"Manes","year":"2009","journal-title":"Eur. Heart. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1465-9921-11-12","article-title":"Pharmacotherapy in pulmonary arterial hypertension: A systematic review and meta-analysis","volume":"11","author":"Ryerson","year":"2010","journal-title":"Respir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/bja\/aep336","article-title":"L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate","volume":"104","author":"Lin","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568016054368214","article-title":"The pharmacologic approach to the prevention of preeclampsia: From antiplatelet, antithrombosis and antioxidant therapy to anticonvulsants","volume":"3","author":"Bar","year":"2005","journal-title":"Curr. Med. Chem. Cardiovasc. Hematol. Agents."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/bcp.12726","article-title":"Pharmacological treatment of acquired QT prolongation and torsades de pointes","volume":"81","author":"Thomas","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"783","DOI":"10.4187\/respcare.05953","article-title":"Medication Regimens for Managing Acute Asthma","volume":"63","author":"Maselli","year":"2018","journal-title":"Respir. Care."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1016\/j.jss.2011.03.028","article-title":"Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats","volume":"171","author":"Kao","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jri.2006.06.004","article-title":"Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFkappaB pathway","volume":"73","author":"Rochelson","year":"2007","journal-title":"J. Reprod. Immunol."},{"key":"ref_18","first-page":"361","article-title":"Effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury","volume":"5","author":"Xu","year":"2002","journal-title":"Chin. J. Traumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.surneu.2005.07.058","article-title":"Magnesium sulfate treatment decreases caspase-3 activity after experimental spinal cord injury in rats","volume":"64","author":"Solaroglu","year":"2005","journal-title":"Surg. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jss.2017.09.005","article-title":"Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium","volume":"221","author":"Chang","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_21","first-page":"472","article-title":"Persistent pulmonary hypertension of the newborn treated with magnesium sulfate in premature neonates","volume":"96","author":"Wu","year":"1995","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/tropej\/fmm101","article-title":"Intravenous magnesium sulphate versus inhaled nitric oxide for moderate, persistent pulmonary hypertension of the newborn. A Multicentre, retrospective study","volume":"54","author":"Raimondi","year":"2008","journal-title":"J. Trop. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1034\/j.1399-6576.2001.045004435.x","article-title":"Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs","volume":"45","author":"Yoshioka","year":"2001","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1152\/jappl.1994.77.2.751","article-title":"Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci","volume":"77","author":"Anderson","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/cs0750661","article-title":"Magnesium aspartate hydrochloride attenuates monocrotaline-induced pulmonary artery hypertension in rats","volume":"75","author":"Mathew","year":"1988","journal-title":"Clin. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/HYPERTENSIONAHA.110.168781","article-title":"Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats","volume":"58","author":"Umar","year":"2011","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jtcvs.2015.05.052","article-title":"Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects","volume":"150","author":"Kishimoto","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3389\/fphys.2016.00517","article-title":"Calcium-Sensing Receptor Regulates Cytosolic [Ca 2+] and Plays a Major Role in the Development of Pulmonary Hypertension","volume":"7","author":"Smith","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.bbamcr.2017.06.018","article-title":"T-type Ca2+ channels elicit pro-proliferative and anti-apoptotic responses through impaired PP2A\/Akt1 signaling in PASMCs from patients with pulmonary arterial hypertension","volume":"1864","author":"Sankhe","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1161\/01.RES.0000189270.72915.D1","article-title":"Ca2+ influx-induced sarcoplasmic reticulum Ca2+ overload causes mitochondrial-dependent apoptosis in ventricular myocytes","volume":"97","author":"Chen","year":"2005","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"L893","DOI":"10.1152\/ajplung.00430.2017","article-title":"Reactive oxygen species induced Ca2+ influx via TRPV4 and microvascular endothelial dysfunction in the SU5416\/hypoxia model of pulmonary arterial hypertension","volume":"314","author":"Suresh","year":"2018","journal-title":"Am. J. Physiol. Lung. Cell. Mol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1161\/CIRCULATIONAHA.104.488486","article-title":"Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension","volume":"111","author":"Sitbon","year":"2005","journal-title":"Circulation"},{"key":"ref_33","first-page":"CD010066","article-title":"Calcium channel blockers for pulmonary arterial hypertension","volume":"9","author":"Fan","year":"2015","journal-title":"Cochrane. Database. Syst. Rev."},{"key":"ref_34","first-page":"CD005588","article-title":"Magnesium sulfate for persistent pulmonary hypertension of the newborn","volume":"3","author":"Ho","year":"2007","journal-title":"Cochrane. Database. Syst. Rev"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/cphy.c100003","article-title":"Experimental and transgenic models of pulmonary hypertension","volume":"1","author":"West","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.pupt.2015.09.007","article-title":"Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: A network approach","volume":"35","author":"Vitorino","year":"2015","journal-title":"Pulm. Pharm. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCHEARTFAILURE.111.966127","article-title":"Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension","volume":"6","author":"Mizuno","year":"2013","journal-title":"Circ. Heart. Fail."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lambert, M., Capuano, V., Olschewski, A., Sabourin, J., Nagaraj, C., Girerd, B., Weatherald, J., Humbert, M., and Antigny, F. (2018). Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103162"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0041-008X(91)90223-2","article-title":"Effect of monocrotaline ingestion on liver, kidney, and lung of rats","volume":"60","author":"Roth","year":"1981","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biocel.2017.05.001","article-title":"Norepinephrine stimulation of alpha1D-adrenoceptor promotes proliferation of pulmonary artery smooth muscle cells via ERK-1\/2 signaling","volume":"88","author":"Liu","year":"2017","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.autneu.2013.03.004","article-title":"Effects of intravenous magnesium infusion on in vivo release of acetylcholine and catecholaminein rat adrenal medulla","volume":"177","author":"Komaki","year":"2013","journal-title":"Auton. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.117.312579","article-title":"Standards and methodological rigor in pulmonary arterial hypertension preclinical and translational research","volume":"122","author":"Provencher","year":"2018","journal-title":"Circ. Res."},{"key":"ref_44","first-page":"1177","article-title":"Magnesium sulfate mitigates acute lung injury in endotoxemia rats","volume":"70","author":"Lee","year":"2011","journal-title":"J. Trauma."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1080\/10641963.2016.1210620","article-title":"Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the erk\/mapk pathway","volume":"39","author":"Gao","year":"2017","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jss.2017.08.054","article-title":"Platonin mitigates vascular hyporeactivity of thoracic aorta in septic rats","volume":"221","author":"Peng","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Stumm, C.L., Halcsik, E., Landgraf, R.G., Camara, N.O., Sogayar, M.C., and Jancar, S. (2014). Lung remodeling in a mouse model of asthma involves a balance between tgf-beta1 and bmp-7. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095959"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00383-005-1580-9","article-title":"Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat","volume":"22","author":"Mogilner","year":"2006","journal-title":"Pediatr. Surg. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1369\/0022155413493912","article-title":"Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction","volume":"61","author":"Christia","year":"2013","journal-title":"J. Histochem. Cytochem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zungu-Edmondson, M., Shults, N.V., Melnyk, O., and Suzuki, Y.J. (2017). Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416\/hypoxia-treated Sprague-Dawley rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182551"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00441-015-2354-x","article-title":"Postnatal development of the bronchiolar club cells of distal airways in the mouse lung: Stereological and molecular biological studies","volume":"364","author":"Karnati","year":"2016","journal-title":"Cell. Tissue. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:21:19Z","timestamp":1760188879000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,18]]},"references-count":51,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20184622"],"URL":"https:\/\/doi.org\/10.3390\/ijms20184622","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,18]]}}}