Abstract 035: Fetal Growth Restriction is Associated with Spontaneous Gestational Hypertension in African Green Monkeys

Abstract

Hypertensive pregnancy disorders, including gestational hypertension (GH) and preeclampsia (PE), are a major cause of worldwide maternal and fetal mortality. The only treatment for PE is delivery of the infant and placenta. Elucidating the cause of GH and PE is critical for improving diagnosis and therapy. This study provides the pregnant African Green Monkey (AGM; Chlorocebus aethiops sabeus ) as the first known nonhuman model of spontaneous GH with pathophysiological characteristics of PE. Here, maternal blood pressures, water balance, renal electrolyte excretion, and fetal birth weight are characterized in AGMs. Following ketamine sedation (15 mg/kg i.m.), systolic blood pressures (SBP) were obtained in AGMs using forearm plethysmography. Animals were defined as normotensive (NT; SBP < 120 mmHg), hypertensive (HT; SBP ≥ 140 mmHg), or GH (SBP increased from non-HT to ≥15 mmHg in 3 rd trimester). Nonpregnant SBP for NT AGMs was 98.7 ± 3.7 mmHg (n = 18), for HT AGMs was 154.7 ± 5.7 mmHg (n = 6), and for GH AGMs was 111.3 ± 6.1 mmHg (n = 7). Third trimester SBP for NT AGMs was 102.9 ± 4.0 mmHg (n = 13), and for GH AGMs was 146.3 ± 4.6 mmHg (n = 7). SBP decreased by 5.2 ± 8.1 mmHg in NT pregnancies (n = 5) and increased 35.0 ± 8.1 mmHg in GH pregnancies (n = 6).There were no differences in water intake or 24-hour urinary Na + /K + excretions among AGMs regardless of group. Infant birth weight was lower in GH AGMs than that of NT AGMs (GH 233.1 ± 27.0 g, n = 5; NT 314.5 ± 16.7 g, n = 7; p<0.05). These data show GH in the AGM is associated with fetal growth restriction, decreased late pregnancy SBP in controls, and increased SBP in GH, similar to human pregnancies. Future studies include examination of renal glomerular structure, placental histopathology and transcriptomics, protein excretions, and plasma PE biomarkers to further establish this animal as a spontaneous model of GH and possibly PE. The AGM, having diverged from the human lineage approximately 29 million years ago, has close genetic homology to humans. This evolutionary history has led to a shared organ physiology, circadian rhythmicity, upright posture, and complex familial and behavior systems with humans, making it a highly translational animal model of hypertensive pregnancy disorders critical to cardiovascular research.