Early life stress (ELS) is an independent risk factor for the development of cardiovascular disease in adulthood in both humans and rodent models. Maternal separation and early weaning (MSEW), a model of ELS, produces mice with an increased risk of cardiovascular dysfunction in adulthood, despite resting blood pressures (BP), heart rates (HR), and body weights comparable to normally reared controls. Autonomic regulation of HR and BP is an important component of the homeostatic response to stress but has not been investigated in MSEW mice. We hypothesized that exposure to MSEW impairs autonomic function at baseline and in response to an acute psychosocial stressor in adult male mice. C57Bl/6J litters were randomly assigned to MSEW or normally reared control conditions. MSEW litters were separated from dams for 4 h on postnatal days (PDs) 2-5, 8 h on PDs 6-16, and weaned at PD 17. Control litters were undisturbed until weaning at PD 21. At 9 weeks old, telemeters were implanted in MSEW (n=16) and control mice (n=12). During cage switch stress (CSS), mice were moved to a soiled, unfamiliar cage for 4 h. HR, systolic BP (SBP), diastolic BP (DBP), and activity (monitored by telemetry) were similar between control and MSEW mice at baseline and during CSS (p>0.05, 2-way ANOVA). Spectral analysis of HR, SBP, and DBP indicated that HR variability (HRV) total power was lower in MSEW mice during the 12 h inactive period compared to controls (18.9±1.1 ms
2
vs. 27.5±3.1 ms
2
; p=0.0033, 2-way ANOVA) at baseline. HRV low frequency (LF) power was also lower during the 12 h inactive period in MSEW mice (4.2±0.4 ms
2
vs.6.6±0.9 ms
2
; p=0.009). At baseline, 12 h and 24 h DBP variability LF/high frequency (HF) ratio, normalized LF, and normalized HF power were lower in the MSEW group (p<0.05, all comparisons). During the final 90 minutes of CSS, MSEW mice had lower HRV total, LF, and HF power compared to controls (p<0.05); although HR, SBP, DBP, and activity remained similar between groups. These data suggest that MSEW mice have impaired autonomic control of HR and DBP and lack the ability to robustly respond and recover from an acute stressor. Reduced responsiveness of the autonomic nervous system may contribute to the increased risk of cardiovascular disease development in adult mice exposed to MSEW.
H2S and Oxytocin Systems in Early Life Stress and Cardiovascular Disease