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Am J Physiol Regul Integr Comp Physiol (February 14, 2002). doi:10.1152/ajpregu.00491.2001
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Articles in PresS, published online ahead of print February 14, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00491.2001
Submitted on August 17, 2001
Accepted on February 12, 2002

Decreased susceptibility of cardiac contractile function to hypoxia-reoxygenation in renin-angiotensinogen double-transgenic rats

Kay-Dietrich Wagner1*, Vanja Eßmann1, Karsten Mydlak2, Manfred Wirth3, Gunnar Gmehling1, Jurgen Bohlender4, Harald M. Stauss1, Joachim Gunther1, Ingolf Schimke2, and Holger Scholz1

1 Abt. Herz-Kreislauf, Johannes-Muller-Institut fur Physiologie, Berlin, Germany
2 Klinik fur Innere Medizin I, Berlin, Germany
3 Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany
4 Max-Delbruck Centrum fur Molekulare Medizin, Berlin, Germany

* To whom correspondence should be addressed. E-mail: kay-dietrich.wagner{at}charite.de.

We tested the hypothesis that the renin-angiotensin system 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 both, human renin and angiotensinogen as transgenes (TGR), was compared. After 15 minutes 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 minutes of reoxygenation. Improved contractility of the papillary muscles from TGR during hypoxia-reoxygenation correlated with increased glutathione peroxidase (GSH-Px) activities and creatine kinase (CK)-MB and CK-BB isoenzyme levels. On the other hand, inhibition of the renin-angiotensin-system with ramipril (1 mg/kg body weight for three weeks) in wild-type animals deteriorated the contractile function of the papillary muscles during reoxygenation compared to untreated rats. These findings suggest that activation of the renin-angiotensin-system protects contractile function of the cardiac muscle against hypoxia-reoxygenation, possibly through changes in CK-isoenzymes and enhanced antioxidant capacity.




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