Angiotensin-converting Enzyme Inhibition Delays Pulmonary Vascular Neointimal Formation

Autor: Wei Zhang, M D Botney, Daniel P. Schuster, Matt Bernstein, Kazushige Okada
Rok vydání: 1998
Předmět:
Male
Pulmonary and Respiratory Medicine
Neointima
Pulmonary Circulation
medicine.medical_specialty
Heart Ventricles
Hypertension
Pulmonary
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
Pulmonary Artery
Critical Care and Intensive Care Medicine
Poisons
Muscle hypertrophy
Rats
Sprague-Dawley
Angiotensin Receptor Antagonists
Tropoelastin
Internal medicine
medicine.artery
Renin–angiotensin system
medicine
Animals
Pneumonectomy
Antihypertensive Agents
In Situ Hybridization
Monocrotaline
Lung
biology
business.industry
Angiotensin-converting enzyme
Hypertrophy
Organ Size
Blotting
Northern
Elastic Tissue
medicine.disease
Pulmonary hypertension
Angiotensin II
Rats
Disease Models
Animal
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Pulmonary artery
biology.protein
Feasibility Studies
Tunica Intima
Tunica Media
business
Cell Division
Procollagen
Zdroj: American Journal of Respiratory and Critical Care Medicine. 158:939-950
ISSN: 1535-4970
1073-449X
Popis: 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.
Databáze: OpenAIRE
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