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Decreased β-adrenoceptor chronotropic response in selenium-deficient mice

Negative crosstalk between iNOS activity and cAMP accumulation

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Abstract

With the aim to study if selenium (Se) deficiency affects the basal frequency and cardiac response to isoproterenol (ISO), mice were fed a Se-deficient diet (Se-) or the same diet supplemented with 0.2 ppm Se as sodium selenite (Se+) for 4 wk. Atria frequency, cyclic AMP (cAMP) accumulation, nitric oxide synthase (NOS) activity, and β-adrenoceptor-binding assay were then examined. Results showed that Se-mice have both a reduction in atria frequency as well as in cAMP content but higher NOS activity levels either at basal or after ISO stimulation. These differences were suppressed by feeding Se-mice with a Se-supplemented diet for 1 wk or by inhibition of inducible nitric oxide synthase (iNOS). Alterations observed after ISO stimulation in atria of Se-mice were not related to a β-adrenoceptor expression modification because specific radioligand-binding parameters in cardiac membranes from Se-mice and Se+ mice were similar. The reduced response on rate and cAMP in atria from Se-mice to direct adenylate cyclase (AC) stimulation by forskolin and the shifted upward levels present in 2-amino-4-methylpyridine-treated Se-mice is in agreement with a negative crosstalk between iNOS activity and AC activity in Se-mice.

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Author notes

  1. Ricardo M. Gómez & Alejandra Habarta

    Present address: Instituto de Bioquímica y Biología Molecular, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900, La Plata, Argentina

Authors and Affiliations

  1. Cátedra de Farmacología, Facultad de Odontología, Universidad de Buenos Aires, 1122, Buenos Aires, Argentina

    Ricardo M. Gómez & Leonor Sterin-Borda

  2. Laboratorio de Trombosis I, Academia Nacional de Medicina, Buenos Aires, Argentina

    Natalia Pacienza, Mirta Schattner & Alejandra Habarta

  3. BARC-East, USDA/ARS/BHNRC/NRFL, Beltsville, MD

    Orville A. Levander

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  1. Ricardo M. Gómez
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  5. Orville A. Levander
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Gómez, R.M., Pacienza, N., Schattner, M. et al. Decreased β-adrenoceptor chronotropic response in selenium-deficient mice. Biol Trace Elem Res 117, 127–138 (2007). https://doi.org/10.1007/BF02698089

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  • DOI: https://doi.org/10.1007/BF02698089

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