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Effects of nisoldipine on endothelin-1- and angiotensin II-induced immediate/early gene expression and protein synthesis in adult rat ventricular cardiomyocytes


, : Effects of nisoldipine on endothelin-1- and angiotensin II-induced immediate/early gene expression and protein synthesis in adult rat ventricular cardiomyocytes. Journal of Cardiovascular Pharmacology 24(1): 13-16

The cellular mechanisms by which dihydropyridine-type calcium antagonists lead to regression of hypertension-related cardiac hypertrophy have not been clarified. We previously showed that angiotensin II (AII) and endothelin-1 (ET-1) induce protein synthesis in isolated adult rat cardiomyocytes, probably through protein kinase C (PKC) as second messenger and the gene product of the early growth response gene-1 (Egr-1) as third messenger. We now show that the dihydropyridine derivative nisoldipine inhibits AII- and ET-1-induced protein synthesis at low concentrations (IC50 7.5 nM for 0.1 microM ET). Induction of c-fos and Egr-1 mRNA by AII and ET was completely blocked by nisoldipine. Therefore, nisoldipine may influence the signal transduction pathway, i.e., through PKC. These results provide a potential pressure-independent mechanism by which nisoldipine may influence development of cardiac hypertrophy.

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PMID: 7521477


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