Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats.
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.
Nakamoto
Takaaki
T
Department of Cardiology and Pneumology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. takanaka@dokkyomed.ac.jp
Harasawa
Hiroshi
H
Akimoto
Kazumi
K
Hirata
Hisato
H
Kaneko
Hiromichi
H
Kaneko
Noboru
N
Sorimachi
Kenji
K
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography / Q000187:drug effects; D016232:Endothelins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics; D000068557:Olmesartan Medoxomil; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011660:Pulmonary Heart Disease / Q000378:metabolism / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D016232:Endothelins; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D000068557:Olmesartan Medoxomil; D003094:Collagen