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Nonhypotensive dose of β-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure

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Abstract

Renal failure causes sympathetic overactivity and inadequate capillary growth in response to cardiomyocyte hypertrophy in experimental renal failure, as well as in uremic patients. In nonuremic animals, sympathetic overactivity was shown to suppress capillary growth. The purpose of this study was to examine whether blockade with α- and β-adrenoblockers ameliorates the capillary deficit that was documented in the hearts of rats with moderate renal failure. Male Sprague–Dawley rats, 3 days after surgical ablation [subtotal nephrectomy (SNX)] or sham operation (sham), were treated with phenoxybenzamine, metoprolol, or a combination of both: After 12 weeks, the hearts were investigated using morphometric and stereologic techniques. The length density of myocardial capillaries was lower (p<0.05) in untreated SNX than in sham (2,786±372 vs 3,397±602 mm/mm3); the decrease was abrogated by metoprolol (3,305±624 mm/mm3), but not by phenoxybenzamin (2,628±480 mm/mm3). The intercapillary distance increased (p<0.05) in SNX (20.5±1.5 μm) and tended to be lower after metoprolol treatment (19.0±1.9 μm). The media area of intramyocardial arterioles was significantly higher in untreated SNX (1,158±1,343 vs 686±771 μm2 in sham). Metoprolol in nonhypotensive doses prevents the capillary deficit in the hearts of rats with moderate renal failure and presents an argument for an important role of sympathetic overactivity in the genesis of the capillary deficit in moderate chronic renal insufficiency.

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Abbreviations

SNX:

Subtotal nephrectomy

PBZ:

Phenoxybenzamine

MET:

Metoprolol

EPO:

Erythropoietin

LVH:

Left ventricular hypertrophy

BP:

Blood pressure

MAP:

Mean arterial blood pressure

SAP:

Systolic arterial blood pressure

DAP:

Diastolic arterial blood pressure

HR:

Heart rate

S-creatinine:

serum creatinine

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The study was supported by the Deutsche Forschungsgemeinschaft (KFO 106, TP 6). The authors thank Z. Antoni, M. Klewer, P. Rieger, S. Söllner, M. Weckbach, and H. Ziebart for excellent technical support.

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Authors and Affiliations

  1. Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054, Erlangen, Germany

    Kerstin Amann & Valentina Câmpean

  2. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    Jürgen Hofstetter, Andreas Koch & Marie-Luise Gross

  3. Department of Medicine IV, University of Erlangen-Nürnberg, Erlangen, Germany

    Roland Veelken

  4. Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany

    Eberhard Ritz

Authors
  1. Kerstin Amann
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  2. Jürgen Hofstetter
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  3. Valentina Câmpean
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  4. Andreas Koch
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  5. Marie-Luise Gross
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  6. Roland Veelken
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  7. Eberhard Ritz
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Correspondence to Kerstin Amann.

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Amann, K., Hofstetter, J., Câmpean, V. et al. Nonhypotensive dose of β-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure. Virchows Arch 449, 207–214 (2006). https://doi.org/10.1007/s00428-006-0219-0

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  • DOI: https://doi.org/10.1007/s00428-006-0219-0

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