|Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation.|
|PMID: 9731029 Owner: NLM Status: MEDLINE|
|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.|
|K Okada; M L Bernstein; W Zhang; D P Schuster; M D Botney|
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|Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.|
|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|
|Created Date: 1998-10-05 Completed Date: 1998-10-05 Revised Date: 2007-11-14|
Medline Journal Info:
|Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: UNITED STATES|
|Languages: eng Pagination: 939-50 Citation Subset: AIM; IM|
|Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents / therapeutic use*
Blood Pressure / drug effects
Disease Models, Animal
Elastic Tissue / pathology
Gene Expression Regulation
Heart Ventricles / pathology
Hypertension, Pulmonary / drug therapy*, etiology, pathology
In Situ Hybridization
Monocrotaline / adverse effects
Poisons / adverse effects
Procollagen / genetics, metabolism
Pulmonary Artery / drug effects*, pathology
Pulmonary Circulation / physiology
Receptors, Angiotensin / antagonists & inhibitors
Tropoelastin / genetics, metabolism
Tunica Intima / drug effects*, pathology
Tunica Media / pathology
|HL-02425/HL/NHLBI NIH HHS; HL-29594/HL/NHLBI NIH HHS|
|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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