title: Enhanced protein phosphorylation in hypertensive hypertrophy.
abstract: OBJECTIVE
  Chronic pressure overload in spontaneously hypertensive rats (SHR) is accompanied by heart hypertrophy and signs of heart failure. Since there is growing evidence for a possible pathophysiological role of altered protein phosphorylation in heart hypertrophy and failure, we studied here cardiac regulatory phosphoproteins and the kinases and phosphatases which regulate their phosphorylation state.
  
  
  METHODS
  The experiments were performed in ventricles of SHR (12-13 weeks old) and age-matched normotensive Wistar-Kyoto rats (WKY).
  
  
  RESULTS
  Basal as well as isoproterenol (Iso)-stimulated force of contraction (FOC) was markedly decreased in isolated electrically driven papillary muscles of SHR. Iso (3 micromol/l, 10 min) increased FOC by 0.91+/-0.20 mN in SHR and by 3.88+/-0.52 mN in WKY, respectively. Ca(2+)-uptake by sarcoplasmic reticulum (SR) at low ionized Ca(2+)-concentration was increased in homogenates from SHR. This was not due to altered expression of phospholamban (PLB), SR-Ca(2+)-ATPase and calsequestrin. However, PLB-phosphorylation at threonine-17 (PLB-PT-17) and the activity of Ca(2+)/calmodulin dependent protein kinase (Ca(2+)/Cam-PK) was increased in SHR. In addition, we found an enhanced protein kinase A (PKA)-dependent phosphorylation of the inhibitory subunit of troponin (TnI). In contrast, there was no difference in the activity or expression (protein- and mRNA-level) of protein phosphatases type 1 or type 2A between SHR and WKY.
  
  
  CONCLUSIONS
  It is suggested that increased Ca(2+)/Cam-PK-activity with resulting increase of PLB-PT-17 enhanced SR-Ca(2+)-uptake in SHR and might contribute to the pathophysiological changes in cardiac hypertrophy of SHR.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Domagkstrasse 12, D-48129 Münster, Germany. boknik@uni-muenster.de
authors.forename: P
authors.initials: P
authors.lastname: Bokník
authors.forename: I
authors.initials: I
authors.lastname: Heinroth-Hoffmann
authors.forename: U
authors.initials: U
authors.lastname: Kirchhefer
authors.forename: J
authors.initials: J
authors.lastname: Knapp
authors.forename: B
authors.initials: B
authors.lastname: Linck
authors.forename: H
authors.initials: H
authors.lastname: Lüss
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
authors.forename: O
authors.initials: O
authors.lastname: Brodde
authors.forename: J
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology*; D006973:Hypertension / Q000150:complications*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D000099211:Phospholamban
chemical_list: D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D007545:Isoproterenol; D010744:Phosphoric Monoester Hydrolases; D011494:Protein Kinases; D000099211:Phospholamban