title: Alpha1-adrenergic stress induces downregulation of Na+/Ca2+ exchanger in myocardial preparations from rabbits at physiological preload.
abstract: Alpha1-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 alpha1-agonist phenylephrine (PE, 10 micromol/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 alpha1-blocker prazosin (13 micromol/L) and the PKC inhibitor GF109203X (1 micromol/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 alpha1-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). alpha1-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 alpha1-adrenergic stimulation.
authors.affiliation: Universitaet Goettingen, Herzzentrum, Kardiologie und Pneumologie, Goettingen, Germany. schiwolf@med.uni-goettingen.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schillinger
authors.forename: Claus
authors.initials: C
authors.lastname: Christians
authors.forename: Samuel
authors.initials: S
authors.lastname: Sossalla
authors.forename: Nils
authors.initials: N
authors.lastname: Teucher
authors.forename: Phuc
authors.initials: P
authors.lastname: Nguyen Van
authors.forename: Harald
authors.initials: H
authors.lastname: Kögler
authors.forename: Oliver
authors.initials: O
authors.lastname: Zeitz
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
mesh_terms: D000818:Animals; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D019831:Sodium-Calcium Exchanger; D013314:Stress, Mechanical; D013315:Stress, Psychological / Q000150:complications*; D016276:Ventricular Function
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D019831:Sodium-Calcium Exchanger