Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy.
We examined the effect of a calcium antagonist, manidipine hydrochloride, on cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP), transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at 3 mg/kg) began 1 day before minipump implantation and continued until the end of the experiments (each group; n = 6). After treatment, left ventricular weight was measured and mRNA was extracted and analyzed by Northern blot hybridization. Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01) without increasing blood pressure. ANP, collagen type I and type III, and fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p < 0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However, TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p < 0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01). Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the expression of genes for ANP and interstitial components of extracellular matrix induced by isoproterenol.
Yoshiyama
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Takeuchi
K
K
Kim
S
S
Hanatani
A
A
Omura
T
T
Toda
I
I
Akioka
K
K
Teragaki
M
M
Iwao
H
H
Yoshikawa
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D015152:Blotting, Northern; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics; D004095:Dihydropyridines / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000737:chemistry; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced* / Q000503:physiopathology*; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D009578:Nitrobenzenes; D009929:Organ Size; D010879:Piperazines; D011674:Pulse; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005353:Fibronectins; D009578:Nitrobenzenes; D010879:Piperazines; D012333:RNA, Messenger; C054218:manidipine; D009320:Atrial Natriuretic Factor; D003094:Collagen; D007545:Isoproterenol