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Altered Water Homeostasis in a Novel Non‐human Primate Model of Gestational Hypertension
Author(s) -
Weaver Chelsea C,
Rhoads Megan K,
Grobe Justin L,
Osborn Jeffrey L
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.692.6
Subject(s) - pregnancy , medicine , blood pressure , gestation , offspring , gestational hypertension , endocrinology , gestational age , fetus , obstetrics , physiology , biology , genetics
De novo maternal hypertension, or gestational hypertension (GH), is a common yet poorly understood complication of pregnancy that may precede pre‐eclampsia (PE). PE affects 5–10% of pregnancies worldwide and may contribute to 40–60% of maternal deaths in underdeveloped countries. The only known treatment of PE is delivery of the offspring and placenta. Understanding the pathogenesis of GH and/or PE, as well as impacts on the fetus and newborn, could provide more effective diagnostics and treatments. At present, no animal model of spontaneous GH or PE has been identified. In this study, we report characteristics of GH and possibly PE in the nonhuman primate Chlorocebus aethiops sabaeus or vervet. GH was defined as a systolic blood pressure (SBP) exceeding 140 mmHg in the second trimester of pregnancy. Systolic blood pressures (SBP) were obtained using forearm plethysmography under ketamine sedation (15 mg/kg i.m.). Animals were characterized as normotensive (NT; SBP < 120 mmHg), borderline hypertensive (BHT; SBP ≥ 120 mmHg and < 140 mmHg), hypertensive (HT; SBP ≥ 140 mmHg), or GH (SBP ≥ 140 mmHg during pregnancy and NT either pre‐ or post‐pregnancy). Non‐pregnant SBP for NT was 119 mmHg (n = 1) and for GH was 107.67 ± 11.46 mmHg (mean ± SEM, n = 3). Peri‐pregnancy SBP for NT was 112 mmHg (n = 1) and for GH was 154.67 ± 6.39 mmHg (mean ± SEM, n = 3). Mean birth weights of babies born to pre‐pregnancy NT mothers was 309.51 ± 10.15 g (n = 4), to pre‐pregnancy HT mothers was 289.52 ± 18.35g (n = 3), and to GH mothers was 179.23 ± 49.23 g (mean ± SEM, n = 2). The average slope of growth rates from birth to 7–16.5 weeks of age for babies born to NT mothers was 34.04 ± 2.00 g/wk (n = 4), to HT mothers was 26.95 ± 1.80 g/wk (n = 3), and to GH mothers was 43.59 ± 2.34 g/wk (mean ± SEM, n = 2). Average daily water consumption for non‐pregnant females was 77.92 ± 23.53 ml/day (n=6) and for pregnant females was 210 ± 18.36 ml/day (mean ± SEM, n=5, p<0.05). Urine flow rate for non‐pregnant females was 65.56 ± 10.40 ml/day (n=6) and for pregnant females was 97.33 ± 13.05 ml/day (n=5, p=0.06). These data suggest significant positive water balance during pregnancy of female vervets, similar to the response in human pregnancies. Future studies include examination of renal glomerular structure, urinary protein excretion, characterization of plasma and urine osmolarity, osmolar excretion, plasma levels of human PE biomarkers including copeptin, sFlt‐1 and PlGF, free water clearance and placental transcriptomics to establish these animals as a novel spontaneous model of PE. Due to the shared organ physiology (eg ‐ placental structure) and close genetic homology to humans, identification of GH and possibly PE in C. aethiops (vervet) provides a highly translational physiological and genomic animal model to study these severe known pathologies of pregnancy. Support or Funding Information Biomedical Science Research Group, LLC and the Gertrude Flora Ribble Foundation