ArticlePloS one2012
Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2 activity and activating NO/PKG pathway in the bile-duct-ligated rat.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Mineralocorticoid Receptor Antagonists for Liver Fibrosis: Potential Mechanisms and Research Progress.Journal of clinical and translational hepatology · 2026Review
- Differential functions of ROCK1 and ROCK2 in liver fibrosis and advances in targeted therapeutic strategies.Frontiers in pharmacology · 2026Review
- Interplay between endocrine disorders and liver dysfunction: Mechanisms of damage and therapeutic approaches.World journal of gastroenterology · 2025Review
- Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy.Cells · 2025Review
- Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation.Hepatology international · 2024Article
- The Idiosyncratic Efficacy of Spironolactone-Loaded PLGA Nanoparticles Against Murine Intestinal Schistosomiasis.International journal of nanomedicine · 2023Article
- Current and investigational drugs in early clinical development for portal hypertension.Frontiers in medicine · 2022Review
- The selective mineralocorticoid receptor antagonist eplerenone prevents decompensation of the liver in cirrhosis.British journal of pharmacology · 2018Article
- Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone.Circulation research · 2018Article
- Mitochondrial dysfunctions contribute to energy deficits in rodent model of hepatic encephalopathy.Metabolic brain disease · 2018Article
- Effects of RAAS Inhibitors in Patients with Kidney Disease.Current hypertension reports · 2017Review
- Novel treatment options for portal hypertension.Gastroenterology report · 2017Article
- Collapsed Reticular Network and its Possible Mechanism during the Initiation and/or Progression of Hepatic Fibrosis.Scientific reports · 2016Article
- Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.World journal of gastroenterology · 2016Article
- Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis.World journal of gastroenterology · 2015Review
- New cellular and molecular targets for the treatment of portal hypertension.Hepatology international · 2015Review
- Sodium ferulate lowers portal pressure in rats with secondary biliary cirrhosis through the RhoA/Rho-kinase signaling pathway: a preliminary study.International journal of molecular medicine · 2014Article
- Direct contribution of vascular mineralocorticoid receptors to blood pressure regulation.Clinical and experimental pharmacology & physiology · 2013Review
- Smooth muscle cell mineralocorticoid receptors: role in vascular function and contribution to cardiovascular disease.Pflugers Archiv : European journal of physiology · 2013Review
- Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging.Biomaterials · 2013Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS), has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension.
methodsLiver cirrhosis was induced by bile duct ligation (BDL). Spironolactone was administered orally (20 mg/kg/d) after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson's trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA) expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR). Portal pressure and intrahepatic resistance were examined in vivo.
resultsTreatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6). Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and the activity of NO effector-protein kinase G (PKG) in the liver.
conclusionSpironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and portal hypertension.
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