Abstract Menopause increases the risk of hypertension in women, yet the factors contributing to this important change remain unclear. Because early life stress has persistent and sex‐specific consequences on health, we hypothesized that ageing reveals the latent effects of neonatal maternal separation (NMS) on cardiovascular homeostasis in female rats. Following birth, rats were either subjected to NMS (3 h/day from postnatal days 3 to 12) or raised under standard conditions (CTRL). Cardiovascular and neuroendocrine functions were evaluated at three distinct ages: young adult (12 weeks), middle‐age (35 weeks) and old (64 weeks). Measurements included hormonal profile (multiplex assay), mean arterial blood pressure (MAP; tail cuff method), activity of the plasma angiotensin‐converting enzymes (ACE and ACE2), and activation of the paraventricular nucleus of the hypothalamus (PVN; FosB immunolabelling). Age‐related decline in 17β‐oestradiol (E 2 ) was greater in NMS rats than CTRL. Age‐related rise in MAP was observed only in NMS; MAP was inversely correlated with E 2 levels in NMS rats but not CTRL. In old females, ACE2 activity was 35% less in NMS than CTRL. ACE2 activity was inversely correlated with MAP in old but not young females, regardless of treatment. In the PVN, the number of FosB expressing cells decreased with age; this effect was greater in NMS females. Experiencing stress during early life is an important determinant of the ageing trajectory of females and reproductive senescence marks a turning point in regulation of cardiovascular function. Disruption of estrogen signaling and/or the renin–angiotensin system are plausible mechanisms by which NMS stress compromises cardiovascular health.
Ambrozio‐Marques et al. (2026) studied this question.