Premium
Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat myocardium
Author(s) -
Turcani Marian,
Thormaehlen Dirk,
Rupp Heinz
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705992
Subject(s) - medicine , pressure overload , endocrinology , muscle hypertrophy , contractility , ventricle , constriction , myosin , frank–starling law of the heart , concentric hypertrophy , diastole , cardiology , chemistry , blood pressure , heart rate , cardiac hypertrophy , stroke volume , biochemistry
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 ( P <0.05). Hypertrophied left ventricles manifested an enhanced overall performance but depressed myocardial contractility. Administration of tedisamil was associated with decreased heart rate ( P <0.05). In contrast, cardiac growth in sham‐operated rats and concentric left ventricular hypertrophy of pressure‐overloaded animals was not significantly altered. Hypertrophied hearts from rats treated with tedisamil expressed more α ‐myosin heavy chains (65±4 versus 57±4%; P <0.05). Also, maximal rate of wall stress rise and decline was higher ( P <0.05) in tedisamil‐treated pressure‐overloaded rats. In the rat model of pressure‐overloaded hypertrophy, tedisamil had no effect on cardiac growth but partially corrected myocardial dysfunction. Postulated mechanism of this effect is the phenotype modification of myosin filaments in hypertrophied myocardium.British Journal of Pharmacology (2004) 143 , 561–572. doi: 10.1038/sj.bjp.0705992