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Published on: September 17, 2015
Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy
M Yoshiyama1, K Takeuchi, S Kim
1First Department of Internal Medicine, Osaka City University Medical School, Japan.
Insights
Manidipine hydrochloride, a calcium antagonist, effectively prevented cardiac hypertrophy and associated gene expression changes in rats. This study highlights its potential in managing heart conditions by inhibiting key molecular pathways.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Isoproterenol infusion is a common model to induce cardiac hypertrophy in rats.
- Gene expression of atrial natriuretic peptide (ANP) and extracellular matrix proteins are key indicators of cardiac remodeling.
Purpose of the Study:
- To investigate the effect of manidipine hydrochloride on isoproterenol-induced cardiac hypertrophy.
- To analyze the impact of manidipine hydrochloride on the expression of ANP, TGF-beta 1, and extracellular matrix genes.
Main Methods:
- Rats were induced with cardiac hypertrophy using isoproterenol infusion.
- Manidipine hydrochloride was administered to assess its protective effects.
- Left ventricular weight and mRNA levels of specific genes were measured using Northern blot hybridization.
Main Results:
- Isoproterenol significantly increased left ventricular weight and expression of ANP, collagen type I and III, and fibronectin mRNA.
- Manidipine hydrochloride treatment prevented the increase in left ventricular weight and normalized the expression of ANP, collagen type I and III, and fibronectin mRNA.
- Transforming growth factor beta 1 (TGF-beta 1), collagen type IV, and laminin mRNA levels were not significantly altered by isoproterenol or manidipine hydrochloride.
Conclusions:
- Manidipine hydrochloride effectively prevents cardiac hypertrophy induced by isoproterenol in rats.
- The drug mitigates changes in the expression of genes related to ANP and interstitial extracellular matrix components.
- Manidipine hydrochloride shows potential as a therapeutic agent for cardiac hypertrophy and remodeling.
Abstract:
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.
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