| Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. | |
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MedLine Citation:
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PMID: 20508210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Most patients with pulmonary arterial hypertension (PAH) die from right heart failure. Beta-adrenergic receptor blockade reduces mortality by about 30% in patients with left-sided systolic heart failure, but is not used in PAH. OBJECTIVES: To assess the effect of the adrenergic receptor blocker carvedilol on the pulmonary circulation and right heart in experimental pulmonary hypertension in rats. METHODS: Angioproliferative pulmonary hypertension was induced in rats by combined exposure to the vascular endothelial growth factor-receptor antagonist SU5416 and hypoxia. Carvedilol treatment was started after establishment of pulmonary hypertension and right heart dysfunction. Measurements and MAIN RESULTS: Compared with vehicle-treated animals, treatment with carvedilol resulted in increased exercise endurance; improved right ventricular (RV) function (increased tricuspid annular plane systolic excursion and decreased RV dilatation); and an increased cardiac output. The morphology of the pulmonary vessels and the RV afterload were not affected by carvedilol. Carvedilol treatment was associated with enhancement of RV fetal gene reactivation, increased protein kinase G (PKG) activity, and a reduction in capillary rarefaction and fibrosis. Metoprolol had similar but less pronounced effects in the SU5416 and hypoxia model. Cardioprotective effects were noted of both carvedilol and metoprolol in the monocrotaline model. In the case of carvedilol, but not metoprolol, part of these effects resulted from a prevention of monocrotaline-induced lung remodeling. CONCLUSIONS: Adrenergic receptor blockade reverses RV remodeling and improves RV function in experimental pulmonary hypertension. Beta-adrenergic receptor blockers are not recommended in humans with PAH before their safety and efficacy are assessed in well-designed clinical trials. |
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Authors:
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Harm J Bogaard; Ramesh Natarajan; Shiro Mizuno; Antonio Abbate; Philip J Chang; Vinh Q Chau; Nicholas N Hoke; Donatas Kraskauskas; Michael Kasper; Fadi N Salloum; Norbert F Voelkel |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-27 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 182 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-10-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 652-60 Citation Subset: AIM; IM |
Affiliation:
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Director of the Victoria Johnson Center for Obstructive Lung Disease Research, Virginia Commonwealth University, 1220 East Broad Street, Richmond, VA 23298, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic Antagonists
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pharmacology* Animals Carbazoles / pharmacology* Disease Models, Animal Hypertension, Pulmonary / chemically induced, drug therapy* Indoles / administration & dosage Male Propanolamines / pharmacology* Pulmonary Circulation / drug effects Pyrroles / administration & dosage Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A / administration & dosage, antagonists & inhibitors Ventricular Dysfunction, Right / chemically induced, drug therapy* Ventricular Remodeling / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic Antagonists; 0/Carbazoles; 0/Indoles; 0/Propanolamines; 0/Pyrroles; 0/SU 5416; 0/Vascular Endothelial Growth Factor A; 72956-09-3/carvedilol |
| Comments/Corrections | |
Comment In:
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Am J Respir Crit Care Med. 2010 Sep 1;182(5):586-8
[PMID:
20802168
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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