ArticleAmerican journal of respiratory and critical care medicine2012
Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
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Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it, 339 citations in OpenAlex.
- Meta-Analysis of Pulmonary Artery Denervation for Treatment of Pulmonary Hypertension.Brazilian journal of cardiovascular surgery · 2022Pooled it
- A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension.The European respiratory journal · 2018Trial
- A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.Critical care (London, England) · 2017Trial
- Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension.The Journal of clinical investigation · 2016Trial
- Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).The American journal of cardiology · 2013Trial
- Beyond the Heart-Lung Axis: A Review of the Crosstalk Between the Hemodynamic, Neurohormonal, and Immune Systems in Pulmonary Hypertension.Comprehensive physiology · 2026Review
- Response Letter: ACE Inhibition in PH-COPD: Severity Stratification Unlocks a Precision Medicine Opportunity.Pulmonary circulation · 2026Article
- Transcriptomic Features of Thyroid Signaling Disorders in Experimental Pulmonary Arterial Hypertension.Bulletin of experimental biology and medicine · 2026Article
- Angiotensin Converting Enzyme Inhibition and Mortality in Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD).Pulmonary circulation · 2026Article
- Depression and Anxiety in Pulmonary Hypertension Associated With Congenital Heart Disease: Pathophysiology and Clinical Implications of the Heart-Brain Axis.Journal of the Saudi Heart Association · 2026Review
- Rab26 promotes hypoxia-induced hyperproliferation of PASMCs by modulating the AT1R-STAT3-YAP axis.Cellular and molecular life sciences : CMLS · 2025Article
- Fenofibrate as a Modulator of the Renin-Angiotensin System in Su/Hx-Induced Pulmonary Arterial Hypertension.International journal of molecular sciences · 2025Article
- The renin-angiotensin system in models of pulmonary arterial hypertension vs primary hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Pulmonary Arterial Hypertension and Left Heart Disease Phenotype: A Challenging Crossroad.Cardiology research · 2025Review
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Cardiorenal Syndrome in Right Heart Failure Due to Pulmonary Arterial Hypertension-The Right Ventricle as a Therapeutic Target to Improve Renal Function.Cardiovascular drugs and therapy · 2025Review
- Pulmonary Arterial Hypertension Induces Compensatory Increase of Left Ventricular Contractility Indexes in Rats in Response to Its Filling Insufficiency.Bulletin of experimental biology and medicine · 2025Article
- Heart Rate Variability in Pulmonary Arterial Hypertension.Pulmonary circulation · 2025Article
- Special Issue: "Enzymes and Enzyme Inhibitors-Applications in Medicine and Diagnosis 2.0".International journal of molecular sciences · 2024Article
- Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.Nature reviews. Nephrology · 2024Review
110 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationalePatients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.
objectivesAssess systemic and pulmonary RAAS activity in patients with iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.
methodsWe collected 79 blood samples from 58 patients with iPAH in the VU University Medical Center Amsterdam (between 2004 and 2010) to determine systemic RAAS activity. MEASUREMENTS AND MAIN
resultsWe observed increased levels of renin, angiotensin (Ang)I, and AngII, which were associated with disease progression (P < 0.05) and mortality (P < 0.05). To determine pulmonary RAAS activity, lung specimens were obtained from patients with iPAH (during lung transplantation, n = 13) and control subjects (during lobectomy or pneumonectomy for cancer, n = 14). Local RAAS activity in pulmonary arteries of patients with iPAH was increased, demonstrated by elevated angiotensin-converting enzyme activity in pulmonary endothelial cells and increased AngII type 1 (AT(1)) receptor expression and signaling. In addition, local RAAS up-regulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT(1) receptor signaling in patients with iPAH compared with control subjects. Finally, to determine the therapeutic potential of RAAS activity, we assessed the chronic effects of an AT(1) receptor antagonist (losartan) in the monocrotaline PAH rat model (60 mg/kg). Losartan delayed disease progression, decreased right ventricular afterload and pulmonary vascular remodeling, and restored right ventricular-arterial coupling in rats with PAH.
conclusionsSystemic and pulmonary RAAS activities are increased in patients with iPAH and are associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.