Angiotensin-converting Enzyme Inhibition Delays Pulmonary Vascular Neointimal Formation
Autor: | Wei Zhang, M D Botney, Daniel P. Schuster, Matt Bernstein, Kazushige Okada |
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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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