Salutary effect of tedisamil on post-ischemic recovery rat heart: involvement of sarcolemmal (Na,K)-ATPase.
The in vitro effect of tedisamil on the specific activity and kinetic parameters of the sarcolemmal (Na,K)-ATPase as well as its ex vivo effect on the (Na,K)-ATPase in the isolated, perfused rat hearts was determined. Five micromol/l of tedisamil was added 5 min before the onset of 30 min global normothermic ischemia followed by 10 min reperfusion. At the conditions of its maximal cardioprotective effect (heart rate reduction, improved postischemic recovery of left ventricular developed pressure), the hearts were immediately used for isolation of sarcolemmal vesicles. In vitro, 1-100 micromol/l of tedisamil produced a concentration-dependent stimulatory effect on (Na,K)-ATPase activity, with a peak seen at 20 micromol/l (p < 0.01), while Mg-dependent ATPase was almost unchanged. Kinetic analysis revealed a significant increase in the affinity of the Na-binding sites on ATPase molecule at 20 micromol/l of tedisamil. These biochemical findings were confirmed by cytochemistry. Moreover, ex vivo experiments revealed that tedisamil rendered the sarcolemmal (Na,K)-ATPase activity to be a more resistant to detrimental effects of ischemia. In conclusion, the cardioprotective action of tedisamil was accompanied with a better preservation of the specific activity of (Na,K)-ATPase.
Dzurba
A
A
Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Ziegelhöffer
A
A
Okruhlicová
L
L
Vrbjar
N
N
Styk
J
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002462:Cell Membrane; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D007150:Immunohistochemistry; D007511:Ischemia; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy; D012508:Sarcolemma / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents; D003521:Cyclopropanes; D012964:Sodium; C059921:tedisamil; D000254:Sodium-Potassium-Exchanging ATPase