Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat myocardium

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Abstract
Reduction in repolarizing potassium currents has controversial effects on hypertrophic responses in cardiomyocytes of transgenic models and cultured cardiomyocytes. It remains thus unknown whether a blockade of potassium channels with tedisamil (N,N′dicyclopropylmethylene‐9,9‐tetramethylene‐3,7‐diazabicyclo(3.3.1)nonane dihydrochloride) has any effects on cardiac growth during postnatal development or pressure overload. To test the hypothesis that a treatment with tedisamil affects cardiac growth or protein phenotype, sham‐operated rats and rats with ascending aorta constriction were treated with tedisamil (36 mg kg day−1) for 7 weeks. Left ventricular mass and geometry, relative expression of myosin isoforms, hydroxyproline concentration and isovolumic ventricular function were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and the diastolic pressure–volume relationship was shifted to smaller volumes. The hydroxyproline concentration remained unaltered. The proportion of α‐myosin heavy chains was, however, reduced (PPα‐myosin heavy chains (65±4 versus 57±4%; PPBritish Journal of Pharmacology (2004) 143, 561–572. doi:10.1038/sj.bjp.0705992

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