Comparative effects of pranidipine with amlodipine in rats with heart failure.
The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.
Veeraveedu
Punniyakoti T
PT
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Watanabe
Kenichi
K
Ma
Meilei
M
Gurusamy
Narasimman
N
Palaniyandi
Suresh S
SS
Wen
Juan
J
Prakash
Paras
P
Wahed
Mir Imam Ibne
MI
Kamal
Fadia A
FA
Mito
Sayaka
S
Kunisaki
Megumi
M
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D024722:Cardiac Myosins; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005355:Fibrosis; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015996:Survival Rate; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; D009320:Atrial Natriuretic Factor; C048161:pranidipine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D024722:Cardiac Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases