Semotiadil improves survival of rats with monocrotaline-induced pulmonary hypertension: comparison with diltiazem.
We compared the effects of semotiadil, a novel Ca2+ channel blocker, with those of diltiazem on survival and regression of right ventricular hypertrophy and media thickening of pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Four weeks later, after pulmonary hypertension was confirmed, oral administration of semotiadil (10, 30, or 100 mg/kg/day) or diltiazem (100 or 300 mg/kg/day) was initiated. The rats were observed for 3 weeks. Survival was significantly longer in the group that received semotiadil 100 mg/kg/day than in the groups treated with diltiazem 100 or 300 mg/kg/day. Media thickness and smooth muscle area in pulmonary arteries were significantly less in rats treated with semotiadil 100 mg/kg/day than in animals treated with diltiazem 100 mg/kg/day. The right ventricle to left ventricle mass ratio, right ventricular wall thickness, and right ventricular myocardial fiber diameter were equal in these two groups. Semotiadil 100 mg/kg/day improved the survival of rats, which responded with a significant regression of right ventricular hypertrophy and media thickening of pulmonary arteries in comparison with rats treated with diltiazem 100 or 300 mg/kg/day.
Takahashi
T
T
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kanda
T
T
Imai
S
S
Suzuki
T
T
Kobayashi
I
I
Murata
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D013844:Thiazoles; D016686:Monocrotaline; C064356:sesamodil; D004110:Diltiazem