Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats.

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.

• Authors: Takaaki Nakamoto, Hiroshi Harasawa, Kazumi Akimoto, Hisato Hirata, Hiromichi Kaneko, Noboru Kaneko, Kenji Sorimachi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 528 Issue 1-3 Pg. 43-51 (Dec 28 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16336959 (Publication Type: Journal Article)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• Endothelins
• Imidazoles
• RNA, Messenger
• Tetrazoles
• Transforming Growth Factor beta
• natriuretic peptide precursor type B, rat
• Natriuretic Peptide, Brain
• Olmesartan Medoxomil
• Collagen

Topics

• Administration, Oral
• Angiotensin II Type 1 Receptor Blockers (administration & dosage, pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Collagen (genetics, metabolism)
• Disease Models, Animal
• Echocardiography (drug effects)
• Endothelins (genetics, metabolism)
• Heart (drug effects)
• Hypertension, Pulmonary (etiology, metabolism, prevention & control)
• Hypertrophy, Right Ventricular (metabolism, prevention & control)
• Hypoxia (complications, drug therapy, metabolism)
• Imidazoles (administration & dosage, pharmacology)
• Lung (drug effects, metabolism, pathology)
• Male
• Myocardium (metabolism, pathology)
• Natriuretic Peptide, Brain (blood, genetics)
• Olmesartan Medoxomil
• Pulmonary Artery (drug effects, metabolism, pathology)
• Pulmonary Heart Disease (metabolism, prevention & control)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Tetrazoles (administration & dosage, pharmacology)
• Transforming Growth Factor beta (genetics, metabolism)