Early life stress induces endothelial dysfunction in a mouse model of maternal separation

Abstract

Early life stress (ELS) is linked to cardiovascular disease in adulthood. We used a mouse model of maternal separation with early weaning (MSEW) to study ELS‐mediated adult cardiovascular pathology. We hypothesized that MSEW induces vascular dysfunction, and sensitizes adult male C57BL/6 mouse to vasoactive factors. MSEW litters were subjected to maternal separation 4h/day (postnatal days (PD) 2–5) and 8h/day (PD6‐16), and weaned at PD17. Control litters were undisturbed until weaning at PD21. We performed wire myography on thoracic aortas of 12‐week‐old mice. MSEW blunted maximum acetylcholine‐induced vasorelaxation (49.8±30.8% vs 72.2±18.4%, p=0.02). Pretreatment (20 min) with apocynin (300μM) and superoxide dismutase (PEG‐SOD, 100 units/ml) reversed this effect. Sodium nitroprusside‐induced vasorelaxation was unaltered by MSEW. Aortas from MSEW mice were hyper‐responsive to phenylephrine‐induced vasoconstriction (61.9±27.0% KCl vs 38.6±18.9% KCl, p=0.04). Baseline SBP (tail‐cuff plethysmography) of MSEW mice was not different from control (109.3±10.9 vs 116.7±20.8mmHg, respectively). Chronic infusion of norepinephrine (7.6μg/kg/min) led to an attenuated hypertensive response in MSEW mice (p≤0.001, main effect). ELS induces classical endothelial dysfunction through an NADPH oxidase‐mediated increase in reactive oxygen species, and a pathological vascular phenotype.PO1 HL 69999