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Impaired coronary function in Wistar Ottawa Karlsburg W rats—a new model of the metabolic syndrome

  • Integrative Physiology
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Abstract

The metabolic syndrome is associated with an increased risk for coronary heart disease. The underlying mechanisms are not well understood. The present study was designed to investigate coronary function in Wistar Ottawa Karlsburg W (WOKW) rats, a new animal model of the metabolic syndrome. The responses of coronary artery segments from WOKW and Dark Agouti (DA) control rats of different ages to several physiological vasoconstrictors and vasodilators were measured in a small vessel wire myograph, and potential mechanisms involved in the differential responses between the two strains were investigated. WOKW showed increased α1-adrenoceptor-mediated coronary constriction at 3 and 10 months of age, as well as seriously blunted β-adrenoceptor-mediated coronary relaxation at 16 months of age. Responses to non-adrenergic agonists were not altered in WOKW compared to DA. The α1-adrenoceptor-mediated coronary constriction in WOKW was completely blocked by rho-kinase inhibition. Induced hyperinsulinemia did not cause increased α1-adrenoceptor-mediated coronary constriction or impaired β-adrenoceptor-mediated coronary relaxation in DA. The association between blunted coronary β-adrenoceptor responsiveness and the metabolic syndrome was confirmed in Zucker diabetic fatty rats. We conclude that the metabolic syndrome in WOKW rats is associated with impaired coronary function due to altered adrenoceptor sensitivity. The latter may contribute to inappropriately elevated coronary tone in insulin-resistant subjects, especially when sympathetic activity to the heart is increased.

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Acknowledgment

This study was supported by the Deutsche Forschungsgemeinschaft grant no. 1430/2–4 and the Department of Cardiovascular Medicine of the University of Greifswald.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Institute of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany

    Olaf Grisk, Tillmann Frauendorf, Torsten Schlüter, Beate Kuttler & Rainer Rettig

  2. Division of Laboratory Animal Science, University of Greifswald, Karlsburg, Germany

    Ingrid Klöting

  3. Institute of Clinical Chemistry, University of Greifswald, Greifswald, Germany

    Alexander Krebs & Jan Lüdemann

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  1. Olaf Grisk
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  2. Tillmann Frauendorf
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Correspondence to Olaf Grisk.

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Grisk, O., Frauendorf, T., Schlüter, T. et al. Impaired coronary function in Wistar Ottawa Karlsburg W rats—a new model of the metabolic syndrome. Pflugers Arch - Eur J Physiol 454, 1011–1021 (2007). https://doi.org/10.1007/s00424-007-0267-6

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  • DOI: https://doi.org/10.1007/s00424-007-0267-6

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