African Green Monkeys Born to Mothers with Hypertensive Pregnancy Disorders have Higher Blood Pressures and Altered Water Balance in Early Adolescence

Abstract

Hypertensive pregnancy disorders are a leading cause of maternal and fetal mortality worldwide. Preeclampsia (PE), or de novo maternal hypertension, is associated with high incidences of preterm birth. Lower birth weight and exposure to hypertension (HTN) in utero have been shown to increase the risk of HTN and cardiovascular disease later in life. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) spontaneously develops gestational hypertension (GH) with pathophysiological similarities to PE, including proteinuria and fetal growth restriction. The AGM also spontaneously develops chronic HTN not associated with pregnancy. We tested the hypothesis that GH and chronic HTN in pregnancy will developmentally program offspring to HTN in adolescence. Male and female juvenile AGMs between the ages of 1 and 2 years were single housed. After a 1‐week acclimation, urine excretion and water intake were measured daily for 3 consecutive days. Blood pressure was measured by forearm plethysmography and fasting blood glucose was assessed. Juvenile AGMs were characterized by maternal systolic blood pressure (SBP) during pregnancy: normotensive (NP; SBP < 120 mmHg throughout pregnancy); hypertensive (HP; SBP > 140 mmHg before, during, and after pregnancy); and gestational hypertensive (GHP; SBP < 120 mmHg before and > 140 mmHg in the second half of pregnancy). Juvenile growth rate was based on body weight from birth to 1–2 years of age. Juvenile growth rates were reduced for GHP and HP compared to NP (NP 1303 g/year; GHP 1083 g/year; HP 946 g/year; p < 0.05). Although animals born to GHP and HP have hindered growth from birth through early adolescence, growth within the first 2 weeks postpartum was greater in GHP animals (34 g/week) compared to NP (15 g/week) and HP (14.6 g/week). Juvenile SBP was higher for HP offspring compared to NP (HP 131.3 ± 11.7 mmHg, n = 3; NP 100.2 ± 9.1 mmHg, n = 5; p < 0.05) but not GHP offspring (GHP 103.4 ± 6.4 mmHg, n = 7; p > 0.05). Diastolic blood pressure (DBP) was higher for HP animals compared to both NP and GHP (HP 67.3 ± 5.7 mmHg, n = 3; NP 45.4 ± 4.4 mmHg, n = 5; GHP 50.7 ± 3.7 mmHg, n = 7; p < 0.05). Fasting glucose tended to be higher in GHP AGM offspring compared to NP and HP, (GHP 111.6 ± 12.1 mg/dL, n = 7; NP 75.4 ± 14.3 mg/dL, n = 5; HP 75.7 ± 18.5 mg/dL, n = 3; p = 0.07). Water intake was similar between NP and GHP (NP 457.5 ± 43.9 ml/day, n = 4; GHP 425.0 ± 13.1 ml/day; p > 0.05). Urine flow was lower in GHP animals compared to NP (NP 146.3 ± 52.0 ml/day vs GHP 77.5 ± 28.2 ml/day, p < 0.05). Thus, adolescent AGMs born to GH pregnancies may have dysregulation of water balance, favoring water retention. This suggests in utero developmental programming may contribute to increased blood pressures later in life. In conclusion, HTN in AGM pregnancy adversely impacts offspring into early adolescence. These insults include hindered growth and susceptibility to HTN. In pregnancy‐induced hypertension, offspring display altered water homeostasis in early adolescence. Continued studies of these NP, HP and GHP offspring will include long‐term blood pressure and heart rate measurements, regulation of sodium and potassium balance, and the further phenotyping of over 50 additional offspring from 2018 births.Support or Funding InformationAHA 17PRE33670127This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.