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Norepinephrine Upregulates Vascular Endothelial Growth Factor in Rat Cardiac Myocytes by a Paracrine Mechanism

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Abstract

Norepinephrine has growth-promoting effects in cardiac myocytes. The present study in cultured neonatal rat cardiac myocytes tested the hypothesis that norepinephrine also stimulates expression of vascular endothelial growth factor (VEGF), an important angiogenic factor. As assessed by polymerase chain reaction cardiac myocytes and non-myocytes expressed all three isoforms of rat VEGF, with the short isoform (VEGF121) preferentially expressed in non-myocytes. When cardiac myocytes were stimulated with 1 μM norepinephrine for 24h in the presence or absence of the specific α- and β-adrenoceptor antagonists prazosin and propranolol, respectively, VEGF mRNA levels and splice variant pattern did not change, whereas atrial natriuretic peptide mRNA levels increased 3 to 4-fold. CoCl2 increased VEGF mRNA levels in cardiac myocytes five-fold. When cardiac myocytes were cultured with conditioned medium from non-myocytes that had been stimulated with norepinephrine for 24 h VEGF mRNA increased 2-fold. The increase was blocked by antibodies neutralizing TGFβ. These data suggest that norepinephrine stimulates myocardial angiogenesis by a paracrine mechanism that involves cardiac non-myocytes and TGFβ.

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Authors and Affiliations

  1. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

    Joachim Weil

  2. Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    Ralf Benndorf & Thomas Eschenhagen

  3. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

    Sabine Fredersdorf & Daniel P. Griese

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  1. Joachim Weil
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  2. Ralf Benndorf
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  5. Thomas Eschenhagen
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Correspondence to Joachim Weil.

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Weil, J., Benndorf, R., Fredersdorf, S. et al. Norepinephrine Upregulates Vascular Endothelial Growth Factor in Rat Cardiac Myocytes by a Paracrine Mechanism. Angiogenesis 6, 303–309 (2003). https://doi.org/10.1023/B:AGEN.0000029411.76494.33

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  • DOI: https://doi.org/10.1023/B:AGEN.0000029411.76494.33

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