{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:45:39Z","timestamp":1792431939797,"version":"4.5.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":550,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1124\/jpet.122.001532","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T21:50:11Z","timestamp":1685051411000},"page":"70-79","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Soluble Guanylyl Cyclase Activator BI 685509 Reduces Portal Hypertension and Portosystemic Shunting in a Rat Thioacetamide-Induced Cirrhosis Model"],"prefix":"10.1016","volume":"386","author":[{"given":"Amanda K.","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khing Jow","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Villalona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"McHugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Zeveleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Brilisauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Bretschneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu Sheng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Fryer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl 5","key":"10.1124\/jpet.122.001532_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2036.16.s5.1.x","article-title":"Review article: albumin in the treatment of liver diseases\u2014new features of a classical treatment","volume":"16","author":"Arroyo","year":"2002","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1124\/jpet.122.001532_bib2","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.3748\/wjg.v20.i10.2555","article-title":"Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis","volume":"20","author":"Bolognesi","year":"2014","journal-title":"World J Gastroenterol"},{"key":"10.1124\/jpet.122.001532_bib3","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1124\/jpet.115.230706","article-title":"A soluble guanylate cyclase activator inhibits the progression of diabetic nephropathy in the ZSF1 rat","volume":"356","author":"Boustany-Kari","year":"2016","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.122.001532_bib4","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1177\/2050640620944140","article-title":"Soluble guanylyl cyclase stimulation and phosphodiesterase-5 inhibition improve portal hypertension and reduce liver fibrosis in bile duct-ligated rats","volume":"8","author":"Brusilovskaya","year":"2020","journal-title":"United European Gastroenterol J"},{"key":"10.1124\/jpet.122.001532_bib5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1681\/ASN.20213210S1264a","article-title":"Phase Ib study of the soluble guanylate cyclase activator BI 685509 in patients with diabetic kidney disease (Abstract)","volume":"32","author":"Cherney","year":"2021","journal-title":"Am Soc Nephrol"},{"key":"10.1124\/jpet.122.001532_bib6","unstructured":"ClinicalTrials.gov (2022). NCT05161481. A study to test whether two different doses of BI 685509 help people with liver cirrhosis and high blood pressure in the portal vein (main vessel going to the liver). https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT05161481. Accessed November 11, 2022."},{"key":"10.1124\/jpet.122.001532_bib7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jhep.2015.05.022","article-title":"Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension","volume":"63","author":"de Franchis","year":"2015","journal-title":"J Hepatol"},{"key":"10.1124\/jpet.122.001532_bib8","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/hep.27376","article-title":"Liver sinusoidal endothelial cells in hepatic fibrosis","volume":"61","author":"DeLeve","year":"2015","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib9","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.3748\/wjg.v20.i23.7260","article-title":"Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: an update","volume":"20","author":"Elpek","year":"2014","journal-title":"World J Gastroenterol"},{"key":"10.1124\/jpet.122.001532_bib10","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/bph.14137","article-title":"The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis","volume":"175","author":"Flores-Costa","year":"2018","journal-title":"Br J Pharmacol"},{"key":"10.1124\/jpet.122.001532_bib11","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jhep.2012.03.007","article-title":"Functional aspects on the pathophysiology of portal hypertension in cirrhosis","volume":"57","author":"Garc\u00eda-Pag\u00e1n","year":"2012","journal-title":"J Hepatol"},{"key":"10.1124\/jpet.122.001532_bib12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/hep.28906","article-title":"Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases","volume":"65","author":"Garcia-Tsao","year":"2017","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S2468-1253(19)30349-8","article-title":"The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"5","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1124\/jpet.122.001532_bib14","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41575-018-0097-3","article-title":"Hepatic microcirculation and mechanisms of portal hypertension","volume":"16","author":"Gracia-Sancho","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1124\/jpet.122.001532_bib15","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1056\/NEJMoa044456","article-title":"Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis","volume":"353","author":"Groszmann","year":"2005","journal-title":"N Engl J Med"},{"key":"10.1124\/jpet.122.001532_bib16","first-page":"9","article-title":"A novel chronic cirrhosis TAA-induced model in rats","volume":"3","author":"Guerra","year":"2010","journal-title":"Braz J Vet Pathol"},{"key":"10.1124\/jpet.122.001532_bib17","doi-asserted-by":"crossref","first-page":"11057","DOI":"10.1073\/pnas.1821045116","article-title":"sGC stimulator praliciguat suppresses stellate cell fibrotic transformation and inhibits fibrosis and inflammation in models of NASH","volume":"116","author":"Hall","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2, Suppl 1","key":"10.1124\/jpet.122.001532_bib18","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.1002\/hep.20993","article-title":"The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule","volume":"43","author":"Iwakiri","year":"2006","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib19","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib20","first-page":"71","article-title":"Nitric oxide-independent activation of soluble guanylate cyclase by BAY 60-2770 in experimental liver fibrosis","volume":"58","author":"Knorr","year":"2008","journal-title":"Arzneimittelforschung"},{"key":"10.1124\/jpet.122.001532_bib21","first-page":"1243A","article-title":"Phase Ib study of the soluble guanylate cyclase activator BI 685509 in patients with mild and moderate hepatic impairment","volume":"74","author":"Lawitz","year":"2021","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1755-1536-6-19","article-title":"Experimental liver fibrosis research: update on animal models, legal issues and translational aspects","volume":"6","author":"Liedtke","year":"2013","journal-title":"Fibrogenesis Tissue Repair"},{"key":"10.1124\/jpet.122.001532_bib23","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.768","article-title":"Modulation of vascular contraction via soluble guanylate cyclase signaling in a novel ex vivo method using rat precision-cut liver slices","volume":"9","author":"Oldenburger","year":"2021","journal-title":"Pharmacol Res Perspect"},{"key":"10.1124\/jpet.122.001532_bib24","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1124\/jpet.122.001532_bib25","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1124\/jpet.122.001423","article-title":"The novel, clinical stage soluble guanylate cyclase activator BI 685509 protects from disease progression in models of renal injury and disease","volume":"384","author":"Reinhart","year":"2023","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.122.001532_bib26","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/liv.15013","article-title":"Outcomes and potential surrogate markers for future clinical trials of non-alcoholic steatohepatitis cirrhosis","volume":"41","author":"Rivera-Esteban","year":"2021","journal-title":"Liver Int"},{"key":"10.1124\/jpet.122.001532_bib27","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3390\/cells9040875","article-title":"Liver fibrosis: mechanistic concepts and therapeutic perspectives","volume":"9","author":"Roehlen","year":"2020","journal-title":"Cells"},{"issue":"Suppl 1","key":"10.1124\/jpet.122.001532_bib28","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.rmed.2016.08.022","article-title":"Anti-fibrotic effects of soluble guanylate cyclase stimulators and activators: a review of the preclinical evidence","volume":"122","author":"Sandner","year":"2017","journal-title":"Respir Med"},{"key":"10.1124\/jpet.122.001532_bib29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/164_2018_197","article-title":"Soluble guanylate cyclase stimulators and activators","volume":"264","author":"Sandner","year":"2021","journal-title":"Handb Exp Pharmacol"},{"key":"10.1124\/jpet.122.001532_bib30","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.3748\/wjg.v24.i38.4356","article-title":"Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension","volume":"24","author":"Schaffner","year":"2018","journal-title":"World J Gastroenterol"},{"key":"10.1124\/jpet.122.001532_bib31","doi-asserted-by":"crossref","first-page":"9372","DOI":"10.1038\/s41598-018-27656-y","article-title":"The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats","volume":"8","author":"Schwabl","year":"2018","journal-title":"Sci Rep"},{"key":"10.1124\/jpet.122.001532_bib32","first-page":"G205","article-title":"Interaction of flow and resistance in maintenance of portal hypertension in a rat model","volume":"250","author":"Sikuler","year":"1986","journal-title":"Am J Physiol"},{"key":"10.1124\/jpet.122.001532_bib33","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.mayocp.2018.12.020","article-title":"Portal hypertension and related complications: diagnosis and management","volume":"94","author":"Simonetto","year":"2019","journal-title":"Mayo Clin Proc"},{"key":"10.1124\/jpet.122.001532_bib34","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/35065611","article-title":"NO-independent regulatory site on soluble guanylate cyclase","volume":"410","author":"Stasch","year":"2001","journal-title":"Nature"},{"key":"10.1124\/jpet.122.001532_bib35","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/sj.bjp.0704483","article-title":"Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies","volume":"135","author":"Stasch","year":"2002","journal-title":"Br J Pharmacol"},{"key":"10.1124\/jpet.122.001532_bib36","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1172\/JCI28371","article-title":"Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels","volume":"116","author":"Stasch","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1124\/jpet.122.001532_bib37","first-page":"G137","article-title":"Quantitation of rat hepatic stellate cell contraction: stellate cells\u2019 contribution to sinusoidal resistance","volume":"277","author":"Thimgan","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1124\/jpet.122.001532_bib38","doi-asserted-by":"crossref","first-page":"8482","DOI":"10.1038\/ncomms9482","article-title":"Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice","volume":"6","author":"Thoonen","year":"2015","journal-title":"Nat Commun"},{"key":"10.1124\/jpet.122.001532_bib39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1124\/jpet.117.247429","article-title":"Pharmacological characterization of IW-1973, a novel soluble guanylate cyclase stimulator with extensive tissue distribution, antihypertensive, anti-inflammatory, and antifibrotic effects in preclinical models of disease","volume":"365","author":"Tobin","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"issue":"1, Suppl","key":"10.1124\/jpet.122.001532_bib40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0023677215573040","article-title":"Standard operating procedures in experimental liver research: thioacetamide model in mice and rats","volume":"49","author":"Wallace","year":"2015","journal-title":"Lab Anim"},{"key":"10.1124\/jpet.122.001532_bib41","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1053\/jhep.2002.31432","article-title":"The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough","volume":"35","author":"Wiest","year":"2002","journal-title":"Hepatology"},{"key":"10.1124\/jpet.122.001532_bib42","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1039\/C5OB00710K","article-title":"The design, synthesis, and biological evaluation of novel YC-1 derivatives as potent anti-hepatic fibrosis agents","volume":"13","author":"Xiao","year":"2015","journal-title":"Org Biomol Chem"},{"key":"10.1124\/jpet.122.001532_bib43","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1053\/j.gastro.2011.12.017","article-title":"Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats","volume":"142","author":"Xie","year":"2012","journal-title":"Gastroenterology"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524170474?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524170474?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.122.001532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T16:51:01Z","timestamp":1740675061000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524170474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["S0022356524170474"],"URL":"https:\/\/doi.org\/10.1124\/jpet.122.001532","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Soluble Guanylyl Cyclase Activator BI 685509 Reduces Portal Hypertension and Portosystemic Shunting in a Rat Thioacetamide-Induced Cirrhosis Model","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.122.001532","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 by The Author(s)","name":"copyright","label":"Copyright"}]}}