Rostafuroxin, the inhibitor of endogenous ouabain, ameliorates chronic undernutrition-induced hypertension, stroke volume, cardiac output, left-ventricular fibrosis and alterations in Na+-transporting ATPases in rats

Figures

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  Fig. 1. Assessment of systolic blood pressure and heart rate at 90 days of age in undernourished and normonourished rats: effect of Rostafuroxin. (A) Systolic blood pressure. (B) Heart rate in conscious rats. (C) Heart rate in anesthetized rats. Diets and treatment or not with Rostafuroxin (Rosta) are indicated on the abscissae. Scatter plots show mean ± SEM. Differences were assayed using two-way ANOVA followed by Bonferroni's test; P values are indicated within the panels. In (A), n = 4, 3, 9, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. In (B), n = 4, 3, 7, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. In (C), n = 5, 5, 8, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. In all cases, n corresponds to one rat. The data of panel A are reproduced from Pereira-Acácio et al. [13] under the terms of Creative Common License CC BY 4.0.

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  Fig. 2. Assessment of body mass, cardiac mass, and cardiac mass/body mass in undernourished and Rostafuroxin-sensitive hypertensive rats: comparison with normonourished animals. (A) Body mass. (B) Cardiac mass. (C) Cardiac mass/Body mass. Diets and treatment or not with Rosta are indicated on the abscissae. Scatter plots show mean ± SEM. Differences were assayed using two-way ANOVA followed by Bonferroni's test; P values are indicated within the panels. In (A), (B), and (C), n = 5, 5, 8, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. In all cases, each n corresponds to one rat.

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  Fig. 3. Measurement of cardiomyocyte area in normonourished and undernourished rats: effect of Rostafuroxin. (A, B, C, and D) Representative immunofluorescence images of pan-cadherin and wheat germ agglutinin lectin of CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. (E) Quantification of cardiomyocyte area. Diets and treatment or not with Rosta are indicated on the abscissa. Scatter plots show mean ± SEM; n = 4, 4, 6, and 6 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta. In all cases, n corresponds to slices from different rats. Differences were assayed using two-way ANOVA mixed effect followed by Bonferroni's test; P values are indicated within the panels.

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  Fig. 4. Measurement of collagen content in normonourished and undernourished rats: effect of Rostafuroxin. (A, B, C, and D) Representative Picrosirius red-stained images of CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. (E) Quantification of collagen content. Diets and treatment or not with Rosta are indicated on the abscissa. Scatter plots show mean ± SEM; n = 4, 4, 4, and 4 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta. In all cases, n corresponds to slices from different rats. Differences were assayed using two-way ANOVA mixed effect followed by Bonferroni's test; P values are indicated within the panels. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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  Fig. 5. Comparison of stroke volume (SV), cardiac output (CO), ejection fraction (EF), fractional shortening (FS), and mitral valve E/A ratio from normonourished and undernourished rats: effect of Rostafuroxin. Diets and treatment or not with Rostafuroxin are indicated on the abscissae. Scatter plots show mean ± SEM. Differences were assayed using two-way ANOVA followed by Bonferroni's test; P values are indicated within the panels. The number of rats (n) was 5, 5, 8, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively (in the study of all echocardiographic parameters). In all cases, each n corresponds to a different rat.

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  Fig. 6. Right renal arterial resistive index (RRI). RRI was calculated as the difference between the peak systolic blood velocity (PSV) and the end diastolic blood velocity (EDV) divided by the peak systolic blood velocity ([PSV - EDV] / PSV). Diets and treatment or not with Rostafuroxin are indicated on the abscissa. Scatter plots show mean ± SEM. Differences were assayed using two-way ANOVA followed by Bonferroni's test; n = 5, 5, 8, and 8 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. In all cases, each n corresponds to a different rat. P values are indicated within the panels.

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  Fig. 7. Different profiles of chronic undernutrition-induced alterations in left ventricle Na+-transporting ATPases: Opposite effects of Rostafuroxin. Diets and treatment or not with Rostafuroxin are indicated on the abscissae. (A) Ouabain-sensitive (Na++K+)ATPase Sens. (B) Ouabain-resistant Na+-ATPase Res. Scatter plots show mean ± SEM. Differences were assayed using two-way ANOVA followed by Bonferroni's test. (A) n = 5 (all groups). (B) n = 6, 5, 4, and 5 for CTRL, CTRL + Rosta, RBD, and RBD + Rosta, respectively. Each n corresponds to a microsomal preparation from 3 (CTRL) and 6 (RBD) hearts of different rats. P values are indicated within the panels. Specific comparisons between groups not covered by two-way ANOVA are indicated in the text.