Ouabain induces cardiac remodeling in rats independent of blood pressure

Abstract

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.

Effect of ouabain on myocardial remodeling in rats

“…In addition, several reports, including the present study, have also demonstrated that there is a correlation between EO and endothelial dysfunction (12,23,24). In the present study, certain significant pathological ultrastructural changes were also identified in rat apical mid-myocardium, in accordance with the findings of a previous study (25). We successfully constructed an experimental animal model of hypertension using intraperitoneal EO injection.…”

Na/K-ATPase Signaling and Salt Sensitivity: The Role of Oxidative Stress

“…Gene replacement studies (in which the ouabain-resistant mouse Na/K-ATPase α1 subunit was replaced with ouabain-sensitive humanized α1 subunit) have unequivocally demonstrated an important role of endogenous CTS in the regulation of renal sodium excretion and BP in rodents [54,55]. CTS also cause significant oxidative stress and cardiovascular remodeling independent of their effect on BP [56,57,58,59]. …”

Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

“…The data suggest that the observed CTS-induced natriuretic effect might be a result of the combined effects of ouabain and MBG [60]. Furthermore, CTS not only induced hypertension in rats but also caused significant cardiovascular remodeling and natriuresis independent of their effect on BP [49, 51, 70, 80, 81]. …”