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 express ion of sodium pump a-subunit isoforms in the myocardium of rats. Methods Normal Sprague-Dawley (SD) rats were injected with ouabain (20 mug . kg(-1) . d(-1), i.p). digoxin (32 mug . 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, an d sodium pump a,-, alpha (-)(2), and alpha (3)-subunit mRNA levels in the m yocardium were detected with the reverse transcription polymerase chain rea ction (RT-PCR) method. Results The systolic blood pressure of the rats infused with ouabain increa sed 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 a-subuni t isoforms in the ventricular myocardium was regulated by either ouabain or digoxin. Both ouabain and digoxin stimulated expression of the alpha (3)-i soform, whereas alpha (2) was unchanged in those two groups. alpha (1)-isof orm expression decreased in the ouabain group and was unchanged in the digo xin group. Conclusions These results suggest that both ouabain and digoxin could regul ate sodium pump a-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.