Altered Glomerular Function is Associated with Spontaneous Gestational Hypertension in African Green Monkeys

Chelsea Christina Weaver; Justin L. Grobe; Mark K. Santillan; Jeffrey L. Osborn

doi:10.1096/fasebj.2018.32.1_supplement.911.9

De novo maternal hypertension, such as preeclampsia (PE) or gestational hypertension (GH), is a major cause of maternal‐fetal mortality worldwide. Poor oxygen delivery to the placenta is associated with fetal growth restriction, low birth weight, reduced immunity, and increased frequency of stillbirths. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) is currently the first known spontaneous model of GH with pathophysiological characteristics of PE. Animals were sedated with ketamine (~15 mg/kg i.m.) and systolic blood pressures (SBP) were obtained via forearm plethysmography. Animals were characterized as normotensive (NT; SBP < 120 mmHg throughout pregnancy) or GH (SBP, non‐HT prior to pregnancy, increased by ≥15 mmHg in 2nd/3rd trimester). Nonpregnant SBP for NT was 98.7 ± 3.7 mmHg (n = 18) and for GH 118.0 ± 6.4 mmHg (n = 16; p>0.05; two way ANOVA). Third trimester SBP for NT did not change, averaging 107.0 ± 10.3 mmHg (n = 5; p>0.05). SBP of GH animals increased 33.0 ± 8.1 mmHg to 151.0 ± 5.0 mmHg (n = 18; p<0.05). SBP, taken within 14 days postpartum (PP) for NT was 107.3 ± 13.8 mmHg (n = 4) and for GH was 112.2 ± 6.6 mmHg (n = 18; p<0.05 GH pregnant vs PP; n = 16). Water intake and urine flow rate did not change with pregnancy or phenotype (p>0.05). Plasma osmolality was not changed in a normal pregnancy (7.6 ± 5.3 mOsm/kg decline; n = 7; p>0.05) but decreased by 27.8 ± 5.8mOsm/kg with GH (n = 10; p<0.05; two way ANOVA), suggesting altered sensitivity to circulating vasopressin in GH. Nonpregnant protein excretion for NT was 472.5 ± 58.0 mg/day (n = 13) and NT third trimester protein excretion rate 501.8 ± 104.6 mg/day (n = 5). Prepregnancy protein excretion for animals that developed GH was 323.2 ± 104.6 mg/day (n = 4; p>0.05) and increased to 650.1 ± 55.9 mg/day in the third trimester (n = 14; p<0.05). Third trimester eGFR (creatinine clearance) averaged 3.9 ± 0.6 ml/min (NT; n = 4) and decreased with GH to 2.4 ± 0.5 ml/min (GH; n = 10; p<0.05). Birth weights of infants born to GH AGMs were less than that of NT AGMs (NT 330.4 ± 21.8 g, n = 7; GH 272.6 ± 14.8 g, n = 13; p<0.05). GH AGMs have significant proteinuria, reduced eGFR during pregnancy, and low birth weight infants. These data suggest altered glomerular and/or tubular function associated with elevated arterial pressure during pregnancy. Future studies include placental histopathology, investigating the role of vasopressin, and establishing plasma PE biomarkers to further explore the pathogenesis of GH in AGM. The AGM is similar to humans regarding organ physiology, comparable placentation, and close evolutionary history. Identification of GH and possibly PE in the AGM provides a highly translational animal model critical to cardiovascular research during gestation and the postpartum period. Support or Funding Information Biomedical Science Research Group, LLC and the American Heart Association Predoctoral Fellowship 17PRE33670127 This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.

Altered Glomerular Function is Associated with Spontaneous Gestational Hypertension in African Green Monkeys

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