ABSTRACT
Objective To compare the effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump α-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 α1-, α2-, and α3-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 α-subunit isoform expression in myocardium were also different: both ouabain and digoxin stimulated expression of α3-isoform whereas α2-isoform unchanged at both mRNA and protein levels. α1-isoform was decreased in ouabain group and α1-isoform unchanged in digoxin group at both mRNA and protein levels. Conclusion It is suggested that both ouabain and digoxin could regulate sodium pump α-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.
ABSTRACT
AIM: To study the effect of ouabain at different concentrations on human vascular endothelial cells (HUVEC), and early endothelial responses to ouabain in physiological concentration by genomic-scale gene expression analysis. METHODS: The proliferation of HUVEC was determined by MTT method. The vitality of cells was determined by LDH, and PCNA was assessed by using immunohistochemistry. The response of endothelial cells to ouabain was explored with a complementary DNA microarray representing ~8 464 different human genes. RESULTS: Ouabain stimulated the proliferation of HUVEC at physiological concentration (0.3-0.9 nmol/L). Ouabain at pathological concentration (0.9-1.8 nmol/L) inhibited proliferation and induced cellular swelling and apoptosis. However, the effect of ouabain at the concentration of 10 nmol/L also stimulated proliferation. The results of mRNA profiles analysis indicated that 340 of genes were differentially expressed, among them 145 were upregulated and 6 were upregulated significantly. The upregulated genes were mainly related to cellular metabolism and gene transcription. CONCLUSIONS: Ouabain has important role in controlling the growth and metabolism of vascular endothelial cell and vascular remodeling in the pathogenesis of hypertension.