Acute Pressor Responses in Mice Exposed to Early Life Stress

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Exposure to adverse childhood experiences, also known as early life stress, is an independent risk factor for the development of cardiovascular disease in adulthood. Previous studies have indicated ELS in rodents may induce impaired blood pressure regulation in response to various pro‐hypertensive stimuli. In the current study, we used maternal separation and early weaning (MSEW), a mouse model of early life stress, to determine the effects of acute behavioral stress on blood pressure regulation (n = 9/group). We utilized exposure to cage switch stress (CSS), a model of acute behavioral stress that subjects mice to a cage previously inhabited by other male mice. MSEW involves maternal separation 4h/day from postnatal days (PD) 2–5 and 8h/day from PD 6–16 then weaned at PD 17. Normally reared litters weaned at PD 21 were used as controls (CON). In normally reared CON and MSEW C57/BL6 male mice, telemetry transmitters were surgically placed with catheters in the carotid artery at 9 weeks of age. After recovery from surgery for 7–10 days, baseline measurements were recorded for 72 hours. Continuous 24 hour systolic and diastolic blood pressures (SBP and DBP) were similar between CON and MSEW mice (SBP: 125 ± 1 vs 121 ± 5 mmHg, p = 0.64; DBP: 89 ± 1 vs 91 ± 1 mmHg, p = 0.24). Additionally, exposure to MSEW did not significantly affect baseline day and night heart rate. We then subjected to CSS for 4 hours. In response to CSS, the peak change in SBP was significantly greater in MSEW mice compared to CON (39 ± 2 vs 27 ± 4 mmHg, respectively, p = 0.02). However, the total pressor response determined by area under the curve for SBP and DBP during the 30 minutes following onset of CSS and 30 minutes following the end of the 4 hour CSS exposure were similar between MSEW and CON mice. Heart rate significantly increased in both MSEW and CON mice compared to baseline (MSEW: 777 ± 10 vs 562 ± 20 bpm, p < 0.0001; CON: 776 ± 4 vs 575 ± 25 bpm, p < 0.0001) and thus the peak change in heart rate was not significantly different between groups (215 ± 18 vs 201 ± 23 bpm, p = 0.64). However, area under the curve analysis indicated MSEW exhibited a blunted heart rate recovery 30 minutes following the end of the 4 hours of exposure to CSS compared to CON (17998 ± 159 vs 18751 ± 287, respectively, p = 0.05). Given the changes in SBP and heart rate following CSS, these data indicate that MSEW mice have an exaggerated pressor response during exposure to acute stress. In conclusion, ELS may predispose exaggerated cardiovascular responses to stress later in life.Support or Funding InformationFunded by NIH grants HL136267 and HL69999 to D.M.P. and J.S.P. and AHA grant 17SFRN33670697 to J.S.P.