Abstract
We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.
MeSH terms
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Administration, Oral
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Angiotensin II Type 1 Receptor Blockers / administration & dosage
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Animals
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Antihypertensive Agents / pharmacology*
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Collagen / genetics
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Collagen / metabolism
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Disease Models, Animal
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Echocardiography / drug effects
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Endothelins / genetics
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Endothelins / metabolism
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Heart / drug effects
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Hypertension, Pulmonary / etiology
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Hypertension, Pulmonary / metabolism
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Hypertension, Pulmonary / prevention & control
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Hypertrophy, Right Ventricular / metabolism
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Hypertrophy, Right Ventricular / prevention & control
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Hypoxia / complications
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Hypoxia / drug therapy*
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Hypoxia / metabolism
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Imidazoles / administration & dosage
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Imidazoles / pharmacology*
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Lung / drug effects
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Lung / metabolism
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Lung / pathology
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Male
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Myocardium / metabolism
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Myocardium / pathology
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Natriuretic Peptide, Brain / blood
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Natriuretic Peptide, Brain / genetics
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Olmesartan Medoxomil
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Pulmonary Artery / drug effects
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Pulmonary Artery / metabolism
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Pulmonary Artery / pathology
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Pulmonary Heart Disease / metabolism
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Pulmonary Heart Disease / prevention & control
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RNA, Messenger / metabolism*
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Rats
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Rats, Wistar
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Tetrazoles / administration & dosage
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Tetrazoles / pharmacology*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
Substances
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Angiotensin II Type 1 Receptor Blockers
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Antihypertensive Agents
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Endothelins
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Imidazoles
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RNA, Messenger
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Tetrazoles
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Transforming Growth Factor beta
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natriuretic peptide precursor type B, rat
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Natriuretic Peptide, Brain
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Olmesartan Medoxomil
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Collagen