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European Journal of Heart Failure 2007 9(4):329-335; doi:10.1016/j.ejheart.2006.10.014
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© 2007 European Society of Cardiology

{alpha}1-adrenergic stress induces downregulation of Na+/Ca2+ exchanger in myocardial preparations from rabbits at physiological preload

Wolfgang Schillingera,*, Claus Christiansa,1, Samuel Sossallaa, Nils Teucherb, Phuc Nguyen Vana, Harald Köglera, Oliver Zeitza,2 and Gerd Hasenfussa

a Universitaet Goettingen, Herzzentrum, Kardiologie und Pneumologie Goettingen, Germany
b Universitaet Goettingen, Herzzentrum, Thorax-, Herz- und Gefaesschirurgie Goettingen, Germany

* Corresponding author. Georg-August-Universität Göttingen, Herzzentrum Göttingen, Kardiologie und Pneumologie, Robert-Koch-Str. 40, 37099 Göttingen, Germany. Tel.: +49 551 39 6349; fax: +49 551 39 9804. E-mail address: schiwolf{at}med.uni-goettingen.de


  Abstract

{alpha}1-adrenergic stimulation and mechanical load are considered crucial for the expression of sarcolemmal Na+/Ca2+ exchanger (NCX1). However, the interaction between these processes is unknown.

We investigated electrically stimulated (1 Hz, 1.75 mmol/L Ca2+) rabbit ventricular trabeculae at physiological preload under stimulation by the selective {alpha}1-agonist phenylephrine (PE, 10 µmol/L). Using quantitative real-time PCR, downregulation of mRNA to 76.5% (p<0.05) was found, while B-type natriuretic peptide (BNP) was increased to 569.5% (p<0.05) compared to control. These changes were abolished in the presence of both the β1-blocker prazosin (13 µmol/L) and the PKC inhibitor GF109203X (1 µmol/L). Furthermore, no changes in NCX mRNA levels under the influence of PE were found in unstretched trabeculae or in unstretched isolated rabbit myocytes (24 h), while BNP was increased in both preparations. In addition, since the {alpha}1-adrenergic effect could be Ca2+-dependent we tested increased extracellular Ca2+ (3.0 mmol/L) in stretched trabeculae and found downregulation of NCX1 to 75.2% (p<0.05).

{alpha}1-stimulation decreases NCX1 mRNA in rabbit myocardium via PKC. This is critically load-dependent and may be mediated by changes in [Ca2+]. In hypertrophy and heart failure, distinct phenotypes with respect to NCX1 expression may result from the interaction between mechanical load and {alpha}1-adrenergic stimulation.

Key Words: Na/Ca exchanger • Hypertrophy • Adrenergic signalling • Mechanical stretch • Rabbits

Received March 25, 2006; Revised July 27, 2006; Accepted October 12, 2006

1 Current address: Klinikum Leverkusen, Klinik fuer Kinder und Jugendliche, Leverkusen Germany.

2 Current address: Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde, Hamburg, Germany.


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