H Reinecke1, R Vetter, H Drexler. 1. Universität Freiburg, Innere Medizin III, Kardiologie und Angiologie, Berlin-Buch, Germany. hreineck@u.washington.edu
Abstract
OBJECTIVE: The cardiac sarcolemmal Na+/Ca(2+)-exchanger (NCX) plays an important role in the maintenance of the myocardial Ca2+ homeostasis which is altered in cardiac hypertrophy and failure. The aim of the present study was to investigate whether alpha-adrenergic stimulation known to induce cardiac hypertrophy might be involved in the regulation of the sarcolemmal NCX. METHODS: Adult rat ventricular cardiocytes (ARC) were isolated from male Sprague-Dawley rats. Phenylephrine, an alpha-adrenergic agonist, was used as hypertrophic agent. NCX expression was measured by competitive RT-PCR and Western blot analysis. RESULTS: alpha-Adrenergic stimulation of ARC with 10 microM phenylephrine for 24 h resulted in a significant increase of the NCX mRNA (2.5-fold) and the NCX protein level (1.8-fold). The changes on the expression level were blocked by the alpha 1-adrenoceptor antagonist prazosin. CONCLUSIONS: The data demonstrate that the NCX expression level is up-regulated by the activation of the alpha-adrenergic signal transduction pathway. The increased NCX mRNA level induced by alpha-adrenergic stimulation appeared to be translated into increased NCX protein level.
OBJECTIVE: The cardiac sarcolemmal Na+/Ca(2+)-exchanger (NCX) plays an important role in the maintenance of the myocardial Ca2+ homeostasis which is altered in cardiac hypertrophy and failure. The aim of the present study was to investigate whether alpha-adrenergic stimulation known to induce cardiac hypertrophy might be involved in the regulation of the sarcolemmal NCX. METHODS: Adult rat ventricular cardiocytes (ARC) were isolated from male Sprague-Dawley rats. Phenylephrine, an alpha-adrenergic agonist, was used as hypertrophic agent. NCX expression was measured by competitive RT-PCR and Western blot analysis. RESULTS: alpha-Adrenergic stimulation of ARC with 10 microM phenylephrine for 24 h resulted in a significant increase of the NCX mRNA (2.5-fold) and the NCX protein level (1.8-fold). The changes on the expression level were blocked by the alpha 1-adrenoceptor antagonist prazosin. CONCLUSIONS: The data demonstrate that the NCX expression level is up-regulated by the activation of the alpha-adrenergic signal transduction pathway. The increased NCX mRNA level induced by alpha-adrenergic stimulation appeared to be translated into increased NCX protein level.