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Development of pressure overload induced cardiac hypertrophy is unaffected by long-term treatment with losartan

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Molecular and Cellular Effects of Nutrition on Disease Processes

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 26))

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Abstract

Left ventricular hypertrophy with adequate wall thickness, preserved adult phenotype and extracellular matrix may be useful in the prevention of heart failure. Because activation of subtype 1 of angiotensin II (AT1) receptors is thought to be involved in the hypertrophic response of cardiomyocytes, we tested the potential of systemic AT1 blockade to modify the development of left ventricular hypertrophy due to pressure overload.

Sham-operated rats and rats with ascending aorta constriction were treated with losartan (30 mg/kg/day) for 8 weeks. Left ventricular geometry, dynamics of isovolumic contractions, hydroxyproline concentration as well as myosin isozymes (marker of fetal phenotype) 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. An enlarged ventricular pressure-volume area and increased (p < 0.05) peak values of+dP/dtmax and-dP/dtmax demonstrated an enhanced overall ventricular performance. Signs of congestive heart failure were not apparent. In contrast, parameters of myocardial function (normalized length-stress area, +dσ/dtmax and -dσ/dtmax) were depressed (p < 0.05), indicating an impaired myocardial contractility. The hydroxyproline concentration remained unaltered. However, the proportion of ²-myosin heavy chains (MHC) was increased (p < 0.05). Administration of losartan decreased (p < 0.05) blood pressure and body weight in sham operated and pressure overloaded rats. By contrast, neither the concentric left ventricular hypertrophy or depressed myocardial function nor the increased ²-MHC expression were significantly altered. Thus, activation of AT1 receptors appears not to be involved in the initial expression of the fetal phenotype of pressure overloaded heart which may be responsible for the progressive functional deterioration of the hypertrophied ventricle. (Mol Cell Biochem 188: 225–233, 1998)

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Author information

Authors and Affiliations

  1. Institute of Pathophysiology, Medical School, Comenius University, Bratislava, Slovak Republic

    Marian Turcani

  2. Molecular Cardiology Laboratory, Division of Cardiology, Philipps University of Marburg, Marburg, Germany

    Heinz Rupp

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  1. Marian Turcani
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  2. Heinz Rupp
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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6

    Grant N. Pierce

  2. Department of Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara Kanagawa 228, Japan

    Tohru Izumi (Professor and Chairman) (Professor and Chairman)

  3. Medizinische Forschung Philipps University of Marburg, Karl-von-Frisch-Str., 135033, Marburg, Germany

    Heinz Rupp

  4. INRA, Lipides Membranaires et Fonctions Cardiovasculaires Faculté des Sciences Pharmaceutiques et Biologiques, 4 Av de l’Observatoire, 75270, Paris Cedex 06, France

    Alain Grynberg

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Turcani, M., Rupp, H. (1998). Development of pressure overload induced cardiac hypertrophy is unaffected by long-term treatment with losartan. In: Pierce, G.N., Izumi, T., Rupp, H., Grynberg, A. (eds) Molecular and Cellular Effects of Nutrition on Disease Processes. Developments in Molecular and Cellular Biochemistry, vol 26. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5763-0_24

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  • DOI: https://doi.org/10.1007/978-1-4615-5763-0_24

  • Publisher Name: Springer, Boston, MA

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