Postpartum Hypertensive Nonhuman Primates Have Decreased Plasma Osmolality without Proteinuria

Abstract

Gestational hypertensive disorders are a leading cause of pregnancy‐related mortality. Postpartum hypertension (PPHT) is a related condition characterized by elevated blood pressure following delivery in previously normotensive (NT) females that returns to normotension within 6 weeks. PPHT is poorly characterized due to its development during a maternal care period lacking direct clinical supervision. We have previously reported spontaneous PPHT in African Green Monkeys (AGM; Chlorocebus aethiops sabaeus). We hypothesize that PPHT in AGM is associated with altered renal function and proteinuria that may lead to long term renal dysfunction. Systolic blood pressures (SBP) were obtained by forearm plethysmography under ketamine sedation (15 mg/kg i.m.) followed by venous blood collection. AGM were classified as NT (SBP ≤ 120 mmHg) or PPHT (NT before and during pregnancy but SBP ≥ 140 mmHg postpartum). Animals were placed in metabolic pens and acclimated for at least 1 week before 3 consecutive days of urine collection. Animals were fed standard nonhuman primate chow and water ad lib. Protein concentrations were measured using a bicinchoninic acid assay. Measurements were taken when nonpregnant (NP), during 3rd trimester of pregnancy (3T, ~14–21 weeks gestation), 1 day postpartum (PP1), 14 days postpartum (PP14), and 42 days postpartum (PP42). Body weights did not differ between NT and PPHT. Water intake for NT and PPHT in NP, 3T and PP did not differ. In NT animals, SBP remained similar to NP SBP during pregnancy and postpartum (NP 104 ± 4.7 mmHg; 3T 99 ± 4.4 mmHg; PP1 102 ± 5.2 mmHg; PP14 101 ± 6.8 mmHg; PP42 97 ± 6.0 mmHg, n=27 per time point). PPHT SBP increased in PP1 compared to NP and 3T (NP 114 ± 10.0 mmHg, n=8; 3T 107 ± 10.0 mmHg, n=8; PP1 144 ± 9.5 mmHg*, n=9; PP14 131 ± 9.0 mmHg*, n=10; PP42 117 ± 10.0 mmHg, n=8; * p≤0.05 vs NP; ANOVA, post hoc SNK). NT protein excretion remained constant though PP14 (NP 365.2 ± 48.5 mg/day, n=26; 3T 473.0 ± 99.0 mg/day, n=8; PP1 501.0 ± 171.4 mg/day, n=6; PP14 387.0 ± 140.0 mg/day, n=7) but declined at PP42 compared to NP (PP42 143.3 ± 171.4 mg/day, n=8; p≤0.05). Furthermore, in PPHT animals protein excretion did not change (NP 421.4 ± 75.5, n=8; 3T 375.4 ± 87.2, n=6; PP1 544.2 ± 71.2, n=9; PP14 578.5 ± 75.5, n=8; PP42 560.8 ± 80.7, n=7). Plasma osmolality was unchanged in NT animals (NP 308.5 ± 4.6 mOsm/kg, n=13; 3T 304.7 ± 6.7 mOsm/kg, n=6; PP1 290.5 ± 8.2 mOsm/kg, n=5; PP14 311.0 ± 11.6 mOsm/kg, n=5; PP42 299.0 ± 16.4 mOsm/kg, n=5). Plasma osmolality of PPHT animals decreased in 3T compared to NP (NP 315.0 ± 7.2 mOsm/kg, n=4; 3T 289.3 ± 5.1 mOsm/kg, n=8; PP1 297.6 ± 4.5 mOsm/kg, n=10; PP14 309.9 ± 5.1 mOsm/kg, n=8; PP42 293.0 ± 5.4 mOsm/kg, n=7; p≤0.05) but returned to NP values by PP14 (p≤0.05). Thus, PPHT in AGM is not associated with renal dysfunction but displays a decrease in plasma osmolality at 3T and elevated postpartum SBP. This decreased plasma osmolality may result from elevated ADH during 3T and may contribute to PPHT. We conclude that PPHT has characteristics of gestational hypertension without altered renal function or 3T hypertension. These data support the AGM as a translational model for acute and long‐term studies of cardiovascular disease in women that develop postpartum hypertension.