| Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation. | |
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MedLine Citation:
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PMID: 9731029 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Primary pulmonary hypertension (PPH) is a disease characterized pathologically by pulmonary artery medial hypertrophy, adventitial thickening, and neointimal proliferation. Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension. |
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Authors:
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K Okada; M L Bernstein; W Zhang; D P Schuster; M D Botney |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 158 ISSN: 1073-449X ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-10-05 Completed Date: 1998-10-05 Revised Date: 2007-11-14 |
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: 939-50 Citation Subset: AIM; IM |
Affiliation:
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Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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therapeutic use* Animals Antihypertensive Agents / therapeutic use* Blood Pressure / drug effects Blotting, Northern Cell Division Disease Models, Animal Elastic Tissue / pathology Feasibility Studies Gene Expression Regulation Heart Ventricles / pathology Hypertension, Pulmonary / drug therapy*, etiology, pathology Hypertrophy In Situ Hybridization Male Monocrotaline / adverse effects Organ Size Pneumonectomy Poisons / adverse effects Procollagen / genetics, metabolism Pulmonary Artery / drug effects*, pathology Pulmonary Circulation / physiology Rats Rats, Sprague-Dawley Receptors, Angiotensin / antagonists & inhibitors Tropoelastin / genetics, metabolism Tunica Intima / drug effects*, pathology Tunica Media / pathology |
| Grant Support | |
ID/Acronym/Agency:
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HL-02425/HL/NHLBI NIH HHS; HL-29594/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Poisons; 0/Procollagen; 0/Receptors, Angiotensin; 0/Tropoelastin; 315-22-0/Monocrotaline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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