Early life stress (ELS) has already been established as an independent risk factor for hypertension and cardiovascular disease, but it remains unclear whether ELS increases the vulnerability to circadian stress later in life. Chronic circadian disruption is known to impair autonomic and hormonal rhythms that support cardiovascular homeostasis. We hypothesize that ELS sensitizes autonomic responses to circadian stressors later in life. We used a maternal separation (MatSep) model of ELS in which newborn pups of Sprague Dawley rats were separated from the dams for 3 hours daily from postnatal day 2 to 14 at the same time of day during the inactive period (10AM – 1PM) and weaned at postnatal day 21. Normally reared (NR) rats were left undisturbed until weaning on day 21. To induce circadian disruption, we used a validated 20-hour day (T20) circadian stress protocol, which causes misalignment of endogenous rhythms due to an inability to entrain to the 10:10 light:dark cycle. At 10 weeks of age, baseline mean arterial pressure (MAP) was measured (telemetry) before exposing both MatSep and NR rats to 5 weeks of T20 circadian stress. Prior to the T20 protocol, NR and MS rats of both sexes had no significant differences in MAP suggesting that MatSep alone has no effect on resting blood pressure. T20 stress did not increase MAP in either NR or MatSep rats but caused loss of diurnal variation in MAP only in both NR and MatSep groups of female rats (pTimeOfDay = 0.028, pMatSep = 0.341, pTODxMatSep = 0.919). However, T20 stress resulted in a decrease in MAP cosinor goodness of fit in only male rats (pT20 = 0.008, pMatSep = 0.579, pT20xMatSep = 0.916), suggesting irregular or non-sinusoidal rhythmicity due to circadian stress. Additionally, all rats maintained diurnal variation in heart rate (HR) at baseline, but female MatSep rats had significantly lower HR compared to NR (pMatSep = 0.005, pTimeOfDay = < 0.001, pMatSepxTOD = 0.516). Following T20 stress, all female rats lost diurnal variation in HR (pMatSep = 0.063, pTimeOfDay = 0.215, pMatSepxTOD = 0.178), but MatSep females continued to exhibit lower HR than NR females in the light phase (379±14 vs. 341±11, respectively, p = 0.019), but not the dark phase. Our findings demonstrate that chronic circadian stress during adulthood disrupts blood pressure and heart rate diurnal variation in only females but causes a loss of sinusoidal rhythmicity in MAP of only male rats. We propose that MatSep-induced ELS primes the cardiovascular system to alter responses to circadian disruptions later in life. Funding: NIH P01 HL158500; U2C/TL1 Deep South KUH PRIME U2C DK133422 & NIH/NIDDK TL1 DK139566 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Aponso et al. (Fri,) studied this question.