Obese Male Mice Exposed to Early Life Stress Display Sympathetic Activation and Hypertension Independent of Circulating Angiotensin II

Figures

• 

  Figure 1. Serum angiotensin peptides in control and MSEW mice fed a low‐fat diet (LFD) and high‐fat diet (HFD). Basal levels of the peptides were not affected by MSEW or diet in male mice: angiotensin I (AngI) (A), angiotensin II (AngII) (B), angiotensin 1‐7 (Ang1‐7) (C), angiotensin 1‐5 (Ang1‐5) (D), and angiotensin III (AngIII) (E). Data were analyzed by 2‐way ANOVA followed by Bonferroni post hoc test and reported as mean±SEM. n=5 per group in LFD‐fed mice, n=8 in HFD‐fed mice. MSEW indicates maternal separation and early weaning.

• 

  Figure 2. Activity of serum renin–angiotensin–aldosterone system (RAAS) components and levels of serum aldosterone in control and MSEW mice fed a low‐fat diet (LFD) and high‐fat diet (HFD). Renin activity (A), and aminopeptidase A (B) were not changed by MSEW or diet; however, aldosterone levels increased similarly in both groups in response to an HFD (C). Data were analyzed by 2‐way ANOVA followed by Bonferroni post hoc test and reported as mean ± SEM. n=5 per group in LFD‐fed mice, n=8 in HFD‐fed mice for renin and aminopeptidase A and n=6 per group for aldosterone. MSEW indicates maternal separation and early weaning.

• 

  Figure 3. Circulating and tissue‐specific angiotensinogen (AGT) in control and MSEW mice fed a low fat diet (LFD) and high fat diet (HFD). Serum (A), liver (B), renal cortex (C), and epididymal white adipose tissue (eWAT) (D). Data were analyzed by 2‐way ANOVA followed by Bonferroni post hoc test and reported as mean±SEM. ** <0.001, *** <0.005, **** <0.0001, *P<0.05 vs C‐LFD; P<0.05 vs respective LFD. n=7 per group in LFD‐fed mice, n=8 in HFD‐fed mice. C‐LFD indicates Control‐LFD; MSEW, maternal separation and early weaning; and NS, no significative.

• 

  Figure 4. Renin–angiotensin–aldosterone system (RAAS) components in epididymal white adipose tissue (eWAT) and renal cortex in control and MSEW mice fed a high‐fat diet (HFD). Angiotensin II (AngII) (A), RAAS expression (B), and angiotensin‐converting enzyme (ACE) and ACE2 activity (C) in eWAT. AngII (D), RAAS components (E), and ACE and ACE2 activity (F) in renal cortex. Data were analyzed by t test. *P<0.05 vs control HFD. n=6–10 per group. AGT indicates angiotensinogen; AT1R, angiotensin type 1 receptor; MSEW, maternal separation and early weaning; Ns, no significative; and RFU, relative fluorescence units.

• 

  Figure 5. Blood pressure in control and MSEW mice fed a high‐fat diet (HFD). A, Enalapril treatment reduced mean arterial pressure (MAP) similarly in both groups. B, Delta blood pressure in response to enalapril treatment. C, Mecamylamine induced a greater reduction in blood pressure regardless the enalapril treatment. Data were analyzed by 1‐way repeated mesures ANOVA followed by Tukey's multiple comparisons test and reported as mean±SEM, n=6. Enal indicates enalapril; MSEW, maternal separation and early weaning; and ns, not significant.

• 

  Figure 6. Acute blood pressure sensitivity to angiotensin II (AngII) before and after angiotensin‐converting enzyme (ACE) inhibition. A, AngII pressor response was reduced control and MSEW enalapril‐treated mice similarly. B, Blood pressure trace in response to a 10 μg/kg AngII dose. Data were analyzed by 1‐way repeated measures ANOVA followed by Tukey's multiple comparisions test and reported as mean±SEM. # P<0.05 vs untreated; & P<0.05 vs untreated, n=6 per group. ENAL indicates enalapril; MAP, mean arterial pressure; MSEW, maternal separation and early weaning; and UT, untreated.