[Differential regulation of sodium pump alpha-subunit isoform gene by ouabain and digoxin in myocardium of rats].
OBJECTIVE
To compare the effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump alpha-subunit expression in myocardium of rats.


METHODS
Normal Sprague-Dawley (SD) rats were injected with ouabain, digoxin or normal saline (NS) everyday and indirect SBP was recorded once a week. Six weeks later, all the rats were killed and sodium pump alpha1-, alpha2-, and alpha3-subunit were detected in the left ventricular myocardium with RT-PCR method and immunohistochemical assay at mRNA and protein levels.


RESULTS
At the end of six weeks SBP of rats infused with ouabain increased significantly (132.6 +/- 9.0 vs 115.7 +/- 8.2 mm Hg, P < 0.01), while no difference of SBP was found between digoxin group and NS group. The effects of ouabain and digoxin on sodium pump alpha-subunit isoform expression in myocardium were also different: both ouabain and digoxin stimulated expression of alpha3-isoform whereas alpha2-isoform unchanged at both mRNA and protein levels. alpha1-isoform was decreased in ouabain group and alpha1-isoform unchanged in digoxin group at both mRNA and protein levels.


CONCLUSIONS
It is suggested that both ouabain and digoxin could regulate sodium pump alpha-subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and might be responsible for the difference between the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.
Yuan
W
W
Department of Cardiology, The First Teaching Hospital, Xi'an Medical University, Xi'an 710061, China.
Wang
H
H
Lü
Z
Z
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D002316:Cardiotonic Agents; D012333:RNA, Messenger; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase