Amlodipine inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.
This study was designed to evaluate the effects of amlodipine, a new calcium channel blocker, on the development of right ventricular hypertrophy and thickening of the media of the pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced in rats by administering a single injection of monocrotaline, 80 mg/kg. The oral administration of amlodipine, 3, 10, or 30 mg/kg/day, was initiated 24 hours later (day 1). On day 28 of therapy, we determined the right ventricular systolic pressure (RVSP), the mass ratio of the right ventricle (RV) to the left ventricle, the thickness of the wall of the RV, the diameter of myocardial fibers in the RV, the percent thickness of the media of the pulmonary artery, and the percent area of smooth muscle in the pulmonary arteries. The magnitude of all parameters was significantly less in the rats administered amlodipine, 30 mg/kg/day, vs. the control group given monocrotaline alone. RVSP, the percent medial thickness, and the percent smooth muscle area, were significantly lower in rats administered a dose of amlodipine, 30 mg/kg/day vs. 10 mg/kg/day. The oral administration of amlodipine, 30 mg/kg/day, inhibited the development of RV hypertrophy and medial thickening of the pulmonary arteries in rats exposed to monocrotaline significantly more effectively vs. the untreated control exposed only to monocrotaline.
Takahashi
T
T
Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
Kanda
T
T
Imai
S
S
Suzuki
T
T
Kobayashi
I
I
Nagai
R
R
D017311:Amlodipine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000517:prevention & control*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D017311:Amlodipine