title: Altered tension cost in (TG(mREN-2)27) rats overexpressing the mouse renin gene.
abstract: The present study aimed to characterize cardiac hypertrophy induced by activation of the renin-angiotensin system in terms of functional alterations on the level of the contractile proteins, employing transgenic rats harboring the mouse renin gene (TGR(mREN2)27). Ca2+-dependent tension and myosin ATPase activity were measured in skinned fiber preparations obtained from TGR(mREN2)27 and from age-matched Sprague-Dawley rats (SPDR). Western blots for troponin I (TnI) and troponin T (TnT) were performed and the phosphorylation status of TnI were evaluated in myocardial preparations. TnT and myosin heavy chain (MHC) isoforms were analyzed by RT-PCR. The pCa/tension relationship was shifted to the right in TGR(mREN2)27 compared to SPDR as indicated by increased Ca2+-concentrations required for half maximal activation of tension (SPDR 5.80, 95% confidence limits 5.77-5.82 vs. TGR(mREN2)27 5.69, 95% confidence limits 5.67-5.72, pCa units), while maximal developed tension was unaltered. Even more pronounced was the shift in the relationship between pCa and myosin-ATPase (SPDR 6.01, 95% confidence limits 5.99-6.03 vs. TGR(mREN2)27 5.77, 95% confidence limits 5.73-5.79, pCa units). The maximal myosin-ATPase activity was reduced in TGR(mREN2)27 compared to SPDR, respectively (211.0 +/- 28.77 micromol ADP/s vs. 271.6 +/- 43.66 micromol ADP/s, P < 0.05). Tension cost (ATPase activity/tension) was significantly reduced in TGR(mREN2)27. The beta-MHC expression was significantly increased in TGR(mREN2)27. There was no isoform shift for TnT (protein and mRNA), as well as TnI, and no alteration of the phosphorylation of TnI in TGR(mREN2)27 compared to SPRD. The present study demonstrates that cardiac hypertrophy, induced by an activation of the renin-angiotensin system, leads to adapting alterations on the level of the contractile filaments, which reduce tension cost.
authors.affiliation: Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Joseph-Stelzmann-Str. 9, 50924, Cologne, Germany. carsten.zobel@uni-koeln.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Zobel
authors.forename: Persephone
authors.initials: P
authors.lastname: Zavidou-Saroti
authors.forename: Birgit
authors.initials: B
authors.lastname: Bölck
authors.forename: Klara
authors.initials: K
authors.lastname: Brixius
authors.forename: Hannes
authors.initials: H
authors.lastname: Reuter
authors.forename: Konrad
authors.initials: K
authors.lastname: Frank
authors.forename: Holger
authors.initials: H
authors.lastname: Diedrichs
authors.forename: Jochen
authors.initials: J
authors.lastname: Müller-Ehmsen
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D007537:Isometric Contraction; D016014:Linear Models; D008297:Male; D051379:Mice; D008955:Models, Cardiovascular; D009129:Muscle Tonus; D009200:Myocardial Contraction; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010210:Papillary Muscles / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
chemical_list: C000594638:MYH7 protein, rat; D012333:RNA, Messenger; C473112:Ren2 protein, mouse; D019210:Troponin I; D020107:Troponin T; D012083:Renin; D018995:Myosin Heavy Chains; D009218:Myosins; D002118:Calcium