{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:50:13Z","timestamp":1785333013831,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T00:00:00Z","timestamp":1473120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31171098"],"award-info":[{"award-number":["31171098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31500929"],"award-info":[{"award-number":["31500929"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Hydrogen sulfide (H2S) is an important endogenous gaseous transmitter in many physiological functions. Plasma H2S decreased, and angiotensin II (Ang II) type 1 receptor (AT1R) increased in the myocardial tissues in 2-kidney 1-clip (2K1C) rats than in normotensive rats. Accumulating evidences suggest that H2S inhibited Ang II\/AT1R pathway to regulate cardiovascular function. Therefore, we hypothesized that H2S may exert beneficial effects on myocardial remodeling in 2K1C rat models of renovascular hypertension.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS AND RESULTS<\/jats:title>\n                  <jats:p>Sodium hydrosulfide (NaHS, 56 \u00b5mol\/kg\/day) was administered intraperitoneally to the rats from the 7th day after 2K1C operation. Systolic blood pressure was significantly increased from the first week after the operation and was lowered after NaHS treatment for 4 weeks. H2S could also inhibit the ratio of left ventricle and septum weight to body weight, improve cross-sectional area, and ameliorate ventricular dysfunction. Additionally, the protein expression of AT1R and Ang II serum content were downregulated, whereas superoxide dismutase (SOD) protein was upregulated in 2K1C rats by NaHS treatment for 4 weeks. Furthermore, the reactive oxygen species level and AT1R protein were increased, whereas SOD protein was decreased in cardiomyocytes treated with Ang II compared with the control group. NaHS could reverse these changes. Losartan and N-acetylcysteine could also reverse Ang II-induced changes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The protective effect of H2S is attributable to the suppression of oxidative stress. This process involves the inhibition of the Ang II\/AT1R pathway and upregulation of antioxidant enzymes in 2K1C rats.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpw104","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T01:55:13Z","timestamp":1473213313000},"page":"67-74","source":"Crossref","is-referenced-by-count":32,"title":["Hydrogen Sulfide Improves Myocardial Remodeling <i>via<\/i> Downregulated Angiotensin \u2161\/AT1R Pathway in Renovascular Hypertensive Rats"],"prefix":"10.1093","volume":"30","author":[{"given":"Shang-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Cui","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"},{"name":"Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University 2 , Shijiazhuang , China ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Mei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medicine, Hebei Medical University 1 , Shijiazhuang , China ;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,9,6]]},"reference":[{"key":"2024020715443692200_CIT0001","first-page":"S436","article-title":"[The role of nitric oxide, hydrogen sulfide and carbon monoxide in the regulation of the circulatory system and their pharmacotherapeutic potential]","volume":"68","author":"Ufnal","year":"2010","journal-title":"Kardiol Pol"},{"key":"2024020715443692200_CIT0002","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.1162667","article-title":"H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase","volume":"322","author":"Yang","year":"2008","journal-title":"Science"},{"key":"2024020715443692200_CIT0003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/CIRCULATIONAHA.109.920991","article-title":"Genetic and pharmacologic hydrogen sulfide therapy attenuates ischemia-induced heart failure in mice","volume":"122","author":"Calvert","year":"2010","journal-title":"Circulation"},{"key":"2024020715443692200_CIT0004","doi-asserted-by":"crossref","first-page":"H451","DOI":"10.1152\/ajpheart.00682.2009","article-title":"H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure","volume":"298","author":"Mishra","year":"2010","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024020715443692200_CIT0005","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/CIRCULATIONAHA.112.000855","article-title":"H2S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase","volume":"127","author":"Kondo","year":"2013","journal-title":"Circulation"},{"key":"2024020715443692200_CIT0006","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1159\/000356602","article-title":"Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK\/NF\u03baB pathway in H9c2 cardiac cells","volume":"32","author":"Guo","year":"2013","journal-title":"Cell Physiol Biochem"},{"key":"2024020715443692200_CIT0007","doi-asserted-by":"crossref","first-page":"e0152838","DOI":"10.1371\/journal.pone.0152838","article-title":"Hydrogen sulfide delays LPS-induced preterm birth in mice via anti-inflammatory pathways","volume":"11","author":"Liu","year":"2016","journal-title":"PLoS One"},{"key":"2024020715443692200_CIT0008","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.pharmthera.2015.12.007","article-title":"Effects of hydrogen sulphide in smooth muscle","volume":"158","author":"Dunn","year":"2016","journal-title":"Pharmacol Ther"},{"key":"2024020715443692200_CIT0009","doi-asserted-by":"crossref","first-page":"H71","DOI":"10.1152\/ajpheart.00574.2014","article-title":"MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery","volume":"310","author":"Kuo","year":"2016","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024020715443692200_CIT0010","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/ars.2010.3517","article-title":"Hydrogen sulfide: neurophysiology and neuropathology","volume":"15","author":"Hu","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"2024020715443692200_CIT0011","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/sj.bjp.0705475","article-title":"Roles of KATP channels in delayed cardioprotection and intracellular Ca(2+) in the rat heart as revealed by kappa-opioid receptor stimulation with U50488H","volume":"140","author":"Chen","year":"2003","journal-title":"Br J Pharmacol"},{"key":"2024020715443692200_CIT0012","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.bbrc.2003.11.130","article-title":"H2S generated by heart in rat and its effects on cardiac function","volume":"313","author":"Geng","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"2024020715443692200_CIT0013","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1056\/NEJMoa013591","article-title":"Endothelial function and oxidative stress in renovascular hypertension","volume":"346","author":"Higashi","year":"2002","journal-title":"N Engl J Med"},{"key":"2024020715443692200_CIT0014","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tig.2004.01.004","article-title":"Human genetics, animal models and computer simulations for studying hypertension","volume":"20","author":"Takahashi","year":"2004","journal-title":"Trends Genet"},{"key":"2024020715443692200_CIT0015","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/ajh.2009.17","article-title":"Oxidative stress in the sympathetic premotor neurons contributes to sympathetic activation in renovascular hypertension","volume":"22","author":"Oliveira-Sales","year":"2009","journal-title":"Am J Hypertens"},{"key":"2024020715443692200_CIT0016","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1161\/01.RES.87.10.840","article-title":"Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress","volume":"87","author":"Cai","year":"2000","journal-title":"Circ Res"},{"key":"2024020715443692200_CIT0017","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/00005344-199903000-00012","article-title":"Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo","volume":"33","author":"Dijkhorst-Oei","year":"1999","journal-title":"J Cardiovasc Pharmacol"},{"key":"2024020715443692200_CIT0018","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1161\/01.HYP.21.6.929","article-title":"Vasodilation to acetylcholine in primary and secondary forms of human hypertension","volume":"21","author":"Taddei","year":"1993","journal-title":"Hypertension"},{"key":"2024020715443692200_CIT0019","doi-asserted-by":"crossref","first-page":"e50102","DOI":"10.1371\/journal.pone.0050102","article-title":"Hydrogen sulfide in paraventricular nucleus enhances sympathetic activity and cardiac sympathetic afferent reflex in chronic heart failure rats","volume":"7","author":"Gan","year":"2012","journal-title":"PLoS One"},{"key":"2024020715443692200_CIT0020","doi-asserted-by":"crossref","first-page":"663","DOI":"10.33549\/physiolres.932848","article-title":"Hydrogen sulfide improves the endothelial dysfunction in renovascular hypertensive rats","volume":"64","author":"Xue","year":"2015","journal-title":"Physiol Res"},{"key":"2024020715443692200_CIT0021","doi-asserted-by":"crossref","first-page":"H2093","DOI":"10.1152\/ajpheart.00088.2007","article-title":"Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats","volume":"293","author":"Shi","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024020715443692200_CIT0022","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1291\/hypres.31.1619","article-title":"Regulatory effect of hydrogen sulfide on vascular collagen content in spontaneously hypertensive rats","volume":"31","author":"Zhao","year":"2008","journal-title":"Hypertens Res"},{"key":"2024020715443692200_CIT0023","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1681\/ASN.2009090949","article-title":"Hydrogen sulfide inhibits plasma renin activity","volume":"21","author":"Lu","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"2024020715443692200_CIT0024","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/jpet.105.092023","article-title":"Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes","volume":"316","author":"Bian","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"2024020715443692200_CIT0025","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1124\/mol.108.047985","article-title":"Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of mitochondrial function","volume":"75","author":"Hu","year":"2009","journal-title":"Mol Pharmacol"},{"key":"2024020715443692200_CIT0026","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/01.RES.50.1.101","article-title":"Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol","volume":"50","author":"Simpson","year":"1982","journal-title":"Circ Res"},{"key":"2024020715443692200_CIT0027","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J Neurosci"},{"key":"2024020715443692200_CIT0028","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.jep.2014.07.006","article-title":"Effects of Xin-Ji-Er-Kang formula on 2K1C-induced hypertension and cardiovascular remodeling in rats","volume":"155","author":"Guo","year":"2014","journal-title":"J Ethnopharmacol"},{"key":"2024020715443692200_CIT0029","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1161\/01.HYP.37.2.371","article-title":"Antisense inhibition of brain renin-angiotensin system decreased blood pressure in chronic 2-kidney, 1 clip hypertensive rats","volume":"37","author":"Kagiyama","year":"2001","journal-title":"Hypertension"},{"key":"2024020715443692200_CIT0030","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00395-015-0477-6","article-title":"ROS and endothelial nitric oxide synthase (eNOS)-dependent trafficking of angiotensin II type 2 receptor begets neuronal NOS in cardiac myocytes","volume":"110","author":"Jang","year":"2015","journal-title":"Basic Res Cardiol"},{"key":"2024020715443692200_CIT0031","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1253\/circj.CJ-10-0892","article-title":"Elevated expression of connective tissue growth factor in human atrial fibrillation and angiotensin II-treated cardiomyocytes","volume":"75","author":"Ko","year":"2011","journal-title":"Circ J"},{"key":"2024020715443692200_CIT0032","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1161\/01.ATV.0000227469.40826.01","article-title":"Role of oxidative stress in remodeling of the myocardial microcirculation in hypertension","volume":"26","author":"Zhu","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024020715443692200_CIT0033","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCRESAHA.116.303697","article-title":"Inflammation, immunity, and hypertensive end-organ damage","volume":"116","author":"McMaster","year":"2015","journal-title":"Circ Res"},{"key":"2024020715443692200_CIT0034","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrd3403","article-title":"Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets","volume":"10","author":"Drummond","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"2024020715443692200_CIT0035","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.febslet.2011.10.048","article-title":"Superoxide dismutases: ancient enzymes and new insights","volume":"586","author":"Miller","year":"2012","journal-title":"FEBS Lett"},{"key":"2024020715443692200_CIT0036","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00424-012-1173-0","article-title":"SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats","volume":"465","author":"Yuan","year":"2013","journal-title":"Pflugers Arch"},{"key":"2024020715443692200_CIT0037","doi-asserted-by":"crossref","first-page":"18434","DOI":"10.1074\/jbc.M409710200","article-title":"G alpha 12\/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes","volume":"280","author":"Nishida","year":"2005","journal-title":"J Biol Chem"},{"key":"2024020715443692200_CIT0038","doi-asserted-by":"crossref","first-page":"23041","DOI":"10.1074\/jbc.M409397200","article-title":"Galpha12\/13-mediated production of reactive oxygen species is critical for angiotensin receptor-induced NFAT activation in cardiac fibroblasts","volume":"280","author":"Fujii","year":"2005","journal-title":"J Biol Chem"},{"key":"2024020715443692200_CIT0039","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.cardiores.2004.08.013","article-title":"Cardiac oxidative stress in acute and chronic isoproterenol-infused rats","volume":"65","author":"Zhang","year":"2005","journal-title":"Cardiovasc Res"},{"key":"2024020715443692200_CIT0040","doi-asserted-by":"crossref","first-page":"15268","DOI":"10.1074\/jbc.M109.076232","article-title":"Pertussis toxin up-regulates angiotensin type 1 receptors through Toll-like receptor 4-mediated Rac activation","volume":"285","author":"Nishida","year":"2010","journal-title":"J Biol Chem"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/1\/67\/2623349","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/1\/67\/2623349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T17:45:28Z","timestamp":1707327928000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/1\/67\/2623349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,6]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,6]]},"published-print":{"date-parts":[[2017,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpw104","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"value":"0895-7061","type":"print"},{"value":"1941-7225","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,1,1]]},"published":{"date-parts":[[2016,9,6]]}}}