Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice

Figures

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  FIGURE 1. Plasma and aortic angiotensin profile in exercise-trained, ACE-I–treated, or after applied combined therapy in Tgαq*44 mice as compared to nontreated and sedentary Tgαq*44 mice. All applied therapies improved the ACE/ACE-2 balance of the RAAS, decreasing concentration of Ang II and III (C and D), and increasing the concentration of alamandine, Ang-(1–7), Ang-(1–9) (E and F), and Ang-(1–10) (A and D). An increased level of Ang-(1–12) in the aorta (B) but not in plasma (A) was also observed. Values were presented as mean ± SEM; n = 4–9. *p < 0.05, **p < 0.01, and ***p < 0.001. Statistics: one-way ANOVA or nonparametric Kruskal–Wallis test between Tg-ExT, Tg-ACE-I, Tg-Sed, and Tg-Exc+ ACE-I for each angiotensin.

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  FIGURE 2. Cardiac function in FVB and Tgαq*44 mice at the end-stage of HF after 8 weeks of treatment [ExT or ExT+ therapy (ACE-I)]. The differences between FVB controls and Tgαq*44 mice (nonrunning and nontreated) were observed in heart rate (A), ejection fraction (B), stroke volume (C), end systolic volume (D), cardiac output (F), isovolumic contraction time (H), early ejection and filling rate (I, J), and atrial filling rate (L). There was a difference in cardiac performance between Tgαq*44 mice with applied ACE-I therapy and sedentary Tgαq*44 mice in left atrial ejection fraction (K). Further, there was a difference in left atrial ejection fraction between sedentary Tgαq*44 mice with applied ACE-I therapy and exercised, nontreated Tgαq*44 mice (K). No other alterations were observed between sedentary and exercised mice (treated or not) from each group (E, G). Sed-sedentary; ExT-exercised; data presented as mean ± SD; n = 7–12. **p < 0.01, ***p < 0.001 for Tgαq*44 (Sed, control) vs. FVB (Sed, control) (t test or Mann–Whitney test). † p < 0.05 for Tgαq*44 (Sed, control) vs. Tgαq*44 (Sed, therapy), ‡ p < 0.05 for Tgαq*44 (Sed, control) vs. Tgαq*44 (ExT, therapy), $ p < 0.05 for Tgαq*44…

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  FIGURE 3. Cardiac reserve under dobutamine stimulation. Chronotropic response to dobutamine was observed in healthy controls, while no chronotropic acceleration was noted in Tgαq*44 mice at the measured stage of HF (A). Cardiac inotropic response to dobutamine was observed in FVB-exercised (as increased FAC) and increased contractility to stimulation was noticed in FVB-exercised and sedentary Tgαq*44 mice with applied therapy (B, C). EDA profoundly decreased after stimulation in sedentary and exercised FVB mice and in sedentary and exercised Tgαq*44 mice with applied therapy (D). Values were presented as mean ± SD; n = 6–12. *p < 0.05, **p < 0.01, and ***p < 0.001 for dobutamine stimulation vs. basal condition. Statistics: t test for comparisons between basal values as compared to values obtained under dobutamine stimulation for each parameter.