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bioRxiv · 10.64898/2026.09.14.751233

Adaptations of the pregnant murine heart to pre-existing hypertension

Ghajar-Rahimi, E.·Shen, A.·Meeks, A.·Kaissar, M.·Faruqi, S.·Stebbings, S.·Castro, J.·Cox, A.·Goergen, C. J.·Yoshida, K.
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Abstract

2-5% of pregnancies are complicated by chronic hypertension [1], increasing the risk of peripartum cardiomyopathy and maternal morbidity [2, 3]. Hypertension reduces stroke volume, whereas pregnancy increases stroke volume. The combined impact of these opposing loads on cardiac function and strain remains unclear. We used a mouse model of pregnancy with pre-existing hypertension to characterize cardiac remodeling. We hypothesized that pregnancy may counteract hypertension-related reductions in cardiac function. Nulliparous female C57Bl6/J mice (7-11 weeks old) were assigned into pregnant (PREG, n=11), angiotensin II-treated (ANGII, n=7), and ANGII+PREG (n=8) groups. Hypertension was induced with subcutaneous angII infusion (1000 ng/kg/min). Cardiac function was measured with high-frequency ultrasound. Ejection fraction (EF) was maintained in PREG animals at 65% but decreased significantly by day 36 in ANGII animals (44.85{+/-}3.27%). In ANGII+PREG mice, EF initially decreased but trended towards PREG values on postpartum day 1. Left ventricle strain was lower in ANGII and ANGII+PREG groups compared to PREG. ANGII and ANGII+PREG animals showed decreased early longitudinal diastolic strain rate at mid-pregnancy compared to baseline (0.82{+/-}0.09% ANGII; 0.73{+/-}0.09% ANGII+PREG), while increasing in PREG (1.76{+/-}0.14%). Minimal physiologically relevant fibrosis was noted across groups via immunohistochemistry. Heart mass-to-body mass was lowest in PREG (6.20{+/-}0.22 mg/g), greatest in ANGII (8.95{+/-}0.39 mg/g), and intermediate in ANGII+PREG (6.92{+/-}0.25 mg/g). Cardiomyocyte cross-sectional area was similar between groups. Overall, pregnancy altered the functional and hypertrophic response to elevated blood pressure. Findings from this work set the foundation for future efforts that may eventually improve cardiovascular care for pregnant patients.

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Ghajar-Rahimi, E., Shen, A., Meeks, A., Kaissar, M., Faruqi, S., Stebbings, S., Castro, J., Cox, A., Goergen, C. J., Yoshida, K.. 2026-09-16. Adaptations of the pregnant murine heart to pre-existing hypertension. https://doi.org/10.64898/2026.09.14.751233

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