Acta Pharmacologica Sinica 2007 March; 28 (3): 344-352; doi: 10.1111/j.1745-7254.2007.00496.x

Aim: To investigate the ouabain's effects on cardiac remodeling in rats.

Methods: Male Sprague-Dawley rats were treated with ouabain. Systolic blood pressure (SBP) was recorded weekly. After 4 and 6 weeks, echocardiography were performed, hemodynamic parameters were measured by invasive cardiac catheterization, changes in cardiac ultrastructure were analyzed using transmission electron microscopy, the collagen fraction of the left ventricle was assessed with Picrosirius red stain, and RT-PCR was applied to evaluate the mRNA level of myosin heavy chain-α and -β in the left ventricle.

Results: Having been treated with ouabain for 4 weeks, there was no significant difference in the mean SBP of the two groups. However, left ventricular hypertrophy, myocardial ultrastructure deterioration, and extracellular matrix remodeling were induced by ouabain treatment; meanwhile, cardiac systolic and diastolic performance were both worsened. Moreover, the cardiac MHC-β mRNA was upregulated by ouabain treatment, whereas MHC-α mRNA was downregulated. After 4 weeks, the mean SBP in the ouabain group began to increase and was significantly higher than that in control group after 6 weeks (P<0.01); the rats' cardiac structure and function were worsened.

Conclusion: These results suggested that ouabain induces alterations in cardiac structure and function, and the effects happened before the increase of blood pressure. The results indicated that ouabain induced cardiac remodeling in rats independent of blood pressure.

Keywords: ouabain; cardiac remodeling; hypertension