抄録
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 β1 (TGF-β1), 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, Ieft 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-β1, 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. (Jpn Cric J 1998; 62: 47 - 52)
