Evaluation of olmesartan medoxomil in the rat monocrotaline model of pulmonary hypertension.
It is suggested that angiotensin II is involved in the pathogenesis of pulmonary hypertension and subsequent right ventricular hypertrophy; therefore, an angiotensin AT1 receptor antagonist could be beneficial for the treatment of this disease. We tested the effect of the new AT1 receptor antagonist olmesartan medoxomil on monocrotaline-induced pulmonary hypertension in rats. At 3 weeks after a single subcutaneous injection of monocrotaline (50 mg/kg), the lung/body weight ratio, the right ventricle/(left ventricle plus septum) weight ratio [RV/(LV+S)], and right ventricular systolic pressure were increased, indicating establishment of pulmonary hypertension and right ventricular hypertrophy. Oral administration of olmesartan medoxomil (2 or 5 mg/kg/day for 3 weeks) restored RV/(LV+S) and right ventricular systolic pressure, and a higher dose (5 mg/kg/day) improved the lung/body weight ratio. Pulmonary arteries isolated from monocrotaline-treated rats exhibited an increase in basal tone in the resting state, indicating that they had intrinsic tone. Three weeks of treatment with olmesartan decreased this intrinsic tone. These data suggest that long-term treatment with olmesartan has beneficial effects on monocrotaline-induced pulmonary hypertension and subsequent right ventricular hypertrophy.
Kato
Tomohiro
T
Department of Veterinary Pharmacology and Anatomy, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
Nasu
Tetsuo
T
Sonoda
Hiroko
H
Ito
Kaoru M
KM
Ikeda
Masahiro
M
Ito
Katsuaki
K
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D000068557:Olmesartan Medoxomil; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D016686:Monocrotaline