Effects of pranidipine, a novel calcium channel antagonist, on the progression of left ventricular dysfunction and remodeling in rats with heart failure.
The cardioprotective properties of pranidipine were studied in a rat model of heart failure after autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were divided into three groups and received oral treatment of 0.03 mg/kg/day (group 0.03) or 0.3 mg/kg/day (group 0.3) of pranidipine or vehicle (group V) for 1 month. High-dose pranidipine (group 0.3) improved the survival rate, and significantly reduced heart weight, heart weight to body weight ratio, myocardial fibrosis, central venous pressure and left ventricular end-diastolic pressure than low-dose pranidipine (group 0.03) and group V. Pranidipine at high dose also decreased the left ventricular systolic and diastolic dimensions, and increased fractional shortening compared with group V. The increase in level of TGF-beta1 and collagen-III mRNA were suppressed by pranidipine in a dose-dependent manner. Our results indicated that pranidipine has cardioprotective effects on heart failure, and that the beneficial effect can be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 and collagen-III mRNA expression, and regression of myocyte hypertrophy.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Kamishin-ei-cho, Japan.
Mir Imam Ibne
MI
Wahed
Kenichi
K
Watanabe
Meilei
M
Ma
Mikio
M
Nakazawa
Toshihiro
T
Takahashi
Go
G
Hasegawa
Makoto
M
Naito
Tadashi
T
Yamamoto
Makoto
M
Kodama
Yushifusa
Y
Aizawa
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000150:complications; D051381:Rats; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016212:Transforming Growth Factor beta; C048161:pranidipine