Differential regulation of the sodium pump alpha-subunit isoform gene by ouabain and digoxin in tissues of rats unit

The effects of ouabain and digoxin on both the systolic blood pressure (SBP ) and sodium pump alpha-subunit expression in some tissues of rats were com pared. Normal rats were injected with ouabain, digoxin, and normal saline ( NS), respectively, everyday, and indirect SEP was recorded once a week. Six weeks later, all the rats were killed, and sodium pump alpha(1)-, alpha(2) -, and alpha(3)-subunit mRNA levels were detected in the myocardium, kidney , adrenal gland, aortic smooth muscle, and hypothalamus by the RT-PCR metho d. The results showed that the SEP of rats infused with ouabain increased s ignificantly at the end of week 6, while no difference in SEP was found bet ween the digoxin and NS groups. The effects of ouabain and digoxin on sodiu m pump alpha-subunit isoform expression were also different. Myocardium: bo th ouabain and digoxin stimulated expression of the alpha(3)-isoform wherea s an was unchanged. Levels of the alpha(1) isoform decreased significantly in the ouabain group and decreased slightly in the digoxin group, respectiv ely. Kidney: digoxin had the same effects as ouabain, alpha(1) levels incre ased, but those of alpha(2) and alpha(3) remained unchanged. Adrenal gland: alpha(2) and alpha(3) levels increased, but those of alpha(1), decreased i n the ouabain group. alpha(1) and alpha(3) levels increased and those of al pha(2) remained unchanged in the digoxin group. Aortic smooth muscle: both ouabain and digoxin increased alpha(1) and alpha(3) expression. alpha(2) le vels decreased in the digoxin group but remained unchanged in the ouabain g roup. Hypothalamus: both ouabain and digoxin stimulated alpha(1) expression , while alpha(2) and alpha(3) levels remained unchanged. The results of thi s study have shown that ouabain and digoxin have the different effects on b oth the systolic blood pressure and expression of sodium pump alpha-subunit isoforms in some tissues in rats. Further studies on the expression of sod ium pump alpha-subunit isoforms might be helpful for the understanding of t he physiological role of endogenous ouabain and the molecular mechanisms in volved in the pathogenesis of hypertension.