Cardioprotection by ouabain and digoxin in perfused rat hearts.
This work was aimed at determining the cardioprotective effect of digitalis glycosides in rat heart, and to relate it with Na, K-ATPase inhibition and ERK1/2 activation. Isolated working rat hearts were perfused in the presence of ouabain or digoxin, which were used at concentrations ranging from 10 to 10 M. The hearts were then subjected to 30 minutes of global normothermic ischemia followed by 120 minutes of retrograde reperfusion; irreversible tissue injury was determined on the basis of triphenyltetrazolium chloride staining. Significant cardioprotection was observed with 10 M and 10 M ouabain (ischemic injury averaged 7.0 +/- 3.5% and 8.3 +/- 0.6% versus 37.3 +/- 2.0% in controls, P < 0.01 in each case). Hearts treated with digoxin showed decreased ischemic injury at 10 M and 10 M (18.0 +/- 1.5% and 14.2 +/- 1.0%, P < 0.01 versus control in both cases). In parallel experiments, ERK2 phosphorylation was increased by 10 to 10 M ouabain, while ERK1 and ERK2 phosphorylation was increased by 10 to 10 M digoxin. The cardioprotective effect was not related to Na, K-ATPase inhibition, since Rbuptake was not significantly different between control and treated hearts.
D'Urso
Giuseppina
G
Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Italy.
Frascarelli
Sabina
S
Zucchi
Riccardo
R
Biver
Tarita
T
Montali
Umberto
U
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004396:Coloring Agents / Q000378:metabolism; D004077:Digoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010042:Ouabain / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts / Q000378:metabolism
D002316:Cardiotonic Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D010042:Ouabain; D004077:Digoxin; C009591:triphenyltetrazolium; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3