EFFECT OF MANIDIPINE HYDROCHLORIDE, A CALCIUM-ANTAGONIST, ON ISOPROTERENOL-INDUCED LEFT-VENTRICULAR HYPERTROPHY

We examined the effect of a calcium antagonist, manidipine hydrochlori de, on cardiac hypertrophy and the expression of the atrial natriureti c 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 is oproterenol (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 weigh t was measured and mRNA was extracted and analyzed by Northern blot hy bridization. Isoproterenol increased left ventricular weight (2.40+/-0 .04 g/kg; p<0.01) without increasing blood pressure. ANP, collagen typ e 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, a nd laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Mani dipine 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.