title: Decreased susceptibility of cardiac function to hypoxia-reoxygenation in renin-angiotensinogen transgenic rats.
abstract: We tested the hypothesis that the renin-angiotensin system (RAS) protects the contractile function of the myocardium against the damaging effect of hypoxia-reoxygenation. For this purpose, the contractility of isolated papillary muscles from wild-type (WT) rats and from rats expressing human renin and angiotensinogen as transgenes (TGR) was compared. After 15 min of hypoxia, peak force (PF) was decreased to 24 +/- 5% of the normoxic values in TGR (n = 10) and to 18 +/- 1% in WT rats (n = 12). PF and relaxation rates recovered completely in TGR but not in WT rats during 45 min of reoxygenation. Improved contractility of the papillary muscles from TGR during hypoxia-reoxygenation correlated with increased glutathione peroxidase activities and creatine kinase (CK)-MB and CK-BB isoenzyme levels. On the other hand, inhibition of the RAS with ramipril (1 mg/kg body wt for 3 wk) in WT animals resulted in deterioration of the contractile function of the papillary muscles during reoxygenation compared with untreated rats. These findings suggest that activation of the RAS protects contractile function of the cardiac muscle against hypoxia-reoxygenation, possibly through changes in CK isoenzymes and enhanced antioxidant capacity.
authors.affiliation: Johannes Müller Institut für Physiologie, Humboldt University, Charité, Tucholskystrasse 2, 10117 Berlin, Germany. kay-dietrich.wagner@charite.de
authors.forename: Kay-Dietrich
authors.initials: KD
authors.lastname: Wagner
authors.forename: Vanja
authors.initials: V
authors.lastname: Essmann
authors.forename: Karsten
authors.initials: K
authors.lastname: Mydlak
authors.forename: Manfred
authors.initials: M
authors.lastname: Wirth
authors.forename: Gunnar
authors.initials: G
authors.lastname: Gmehling
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bohlender
authors.forename: Harald M
authors.initials: HM
authors.lastname: Stauss
authors.forename: Joachim
authors.initials: J
authors.lastname: Günther
authors.forename: Ingolf
authors.initials: I
authors.lastname: Schimke
authors.forename: Holger
authors.initials: H
authors.lastname: Scholz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D006360:Heat-Shock Proteins; D007527:Isoenzymes; D010088:Oxidoreductases; D003402:Creatine Kinase; D010100:Oxygen