Effects of ouabain and digoxin on gene expression of sodium pump alpha-subunit isoforms in rat myocardium.
OBJECTIVE
To compare the effects of ouabain and digoxin on the gene expression of sodium pump alpha-subunit isoforms in the myocardium of rats.


METHODS
Normal Sprague-Dawley (SD) rats were injected with ouabain (20 micrograms.kg-1.d-1, i.p.), digoxin (32 micrograms.kg-1.d-1, i.p.) and normal saline (NS) once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later, all of the rats were killed, and sodium pump alpha 1-, alpha 2-, and alpha 3-subunit mRNA levels in the myocardium were detected with the reverse transcription polymerase chain reaction (RT-PCR) method.


RESULTS
The systolic blood pressure of the rats infused with ouabain increased significantly at the end of week 6 (132.6 +/- 9.0 mm Hg vs 115.7 +/- 8.2 mm Hg, P < 0.01), while no difference in blood pressure was found between the digoxin group and the NS group. The expression of sodium pump alpha-subunit isoforms in the ventricular myocardium was regulated by either ouabain or digoxin. Both ouabain and digoxin stimulated expression of the alpha 3-isoform, whereas alpha 2 was unchanged in those two groups. alpha 1-isoform expression decreased in the ouabain group and was unchanged in the digoxin group.


CONCLUSIONS
These results suggest 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 in the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.
Wang
H
H
Department of Cardiology, First Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Yuan
W
W
Lu
Z
Z
D000818:Animals; D004077:Digoxin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D013599:Systole / Q000187:drug effects
D021122:Protein Subunits; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase