Antihypertensive drugs reduce noradrenaline-induced hypertrophy of cultured myocardial cells.
The cellular mechanisms of cardiac hypertrophy are still largely unknown. In-vivo studies have demonstrated that antihypertensive drugs can regress hypertrophy independently of reductions in blood pressure. The antihypertrophic effects of metoprolol, propranolol, felodipine, verapamil and captopril were studied in neonatal cardiac myocyte culture. Prazosin was used as a positive control. Hypertrophy was defined as an increase in protein content measured by [3H]leucine incorporation. Noradrenaline induced a 1.5-fold increase in protein synthesis over 48 h. Prazosin prevented the hypertrophic effect of noradrenaline. Adrenergic beta-receptor blocking agents and calcium antagonists reduced myocyte hypertrophy in a dose-dependent manner. The angiotensin-converting enzyme inhibitor captopril was ineffective. These results indicate that adrenergic beta-receptor blockers and calcium antagonists may have direct nonhaemodynamic effects on the growth of cultured cardiac myocytes.
Lähteenmäki
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Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Sievi
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Vapaatalo
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015736:Felodipine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007930:Leucine / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats
D000959:Antihypertensive Agents; D011433:Propranolol; D008790:Metoprolol; D007930:Leucine; D015736:Felodipine; D009638:Norepinephrine