Sexual dimorphism of blood pressure responses to angiotensin II in rats subjected to early life circadian stress

Various forms of early life stress (ELS) lead to a greater risk of hypertension, but no studies have examined stress produced by circadian disruption. We hypothesize that circadian stress during adolescence will increase sensitivity to a hypertensive stimulus in adulthood recapitulating other models of ELS. We exposed male and female Sprague-Dawley rats 1-2 weeks post-weaning to 6-hour phase advances (shifts) in the light/dark cycle every 4 days for 4 weeks. At 10-12 weeks of age, baseline mean arterial pressure (MAP) was measured (telemetry) followed by a 2-wk angiotensin II (Ang II) infusion (250 ng/kg/min, s.c.). At baseline, normally reared (NR) and ELS rats of both sexes had no significant differences in MAP suggesting that exposure to circadian stress early in life has no effect on baseline blood pressure. Ang II increased MAP in all groups except of female ELS rats (p ELS =0.0583, p AngII =0.0011, p ELSxAngII =0.1712). Additionally, Ang II resulted in MAP arrhythmicity in only male NR rats (p Zero-amp. =0.78267). We also observed significant phase advance in peak MAP in male ELS rats that was absent in NR (p ELS =0.1171, p AngII =0.0232, p ELSxAngII =0.0131). In contrast, there were no significant differences in rhythmicity or peak MAP time of either female rat groups. Additionally, baseline heartrate (HR) of NR and ELS of either sex had no significant difference. However, Ang II significantly increase HR in only male rats, indicating a heightened sensitivity to stress in males independent of ELS (p ELS =0.4628, p AngII <0.0001, p ELSxAngII =0.1787). While circadian stress in the post-weaning period did affect the MAP response to chronic Ang II as predicted, Ang II produced changes in peak MAP times and HR in male but not female rats. We also propose that circadian stress during the post-weaning period disrupts regulatory responses to Ang II in a sex-specific manner. Funding: NIH P01 HL158500 This abstract was presented at the American Physiology Summit 2025 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.