Abstract P3038: Reduced Renal Responsiveness and Altered Fluid Volume in an African Green Monkey ( Chlorocebus Aethiops Sabaeus) Preeclampsia Model

Abstract

Preeclampsia is a prevalent, multi-organ complication of late pregnancy characterized by de novo gestational hypertension (GH) and proteinuria. Our group has demonstrated that arginine vasopressin (AVP) secretion, as measured by copeptin, is predictive of the development of human preeclampsia. Altered regulation of AVP early in gestation has been demonstrated in human preeclampsia. Recently, the nonhuman primate, African Green Monkey (AGM) has been characterized as a spontaneous, translational model of chronic hypertension, GH and preeclampsia. AGMs also have similar gestation and placentation to humans. We hypothesized that the AGM model of preeclampsia would demonstrate similar AVP related plasma and fluid volume changes as humans with preeclampsia. AGMs (n=10) were anesthetized with ketamine during late third trimester of pregnancy to obtain physiologic and obstetric measurements. Compared to normotensive (NT, n=4) third trimester pregnant females, GH females (n=6) had higher systolic and diastolic blood pressures (106 ± 5 vs. 162 ± 11 mmHg; 46 ± 4 vs. 86 ± 12, p=0.01) with no differences in heart rates (158 ± 4 vs. 169 ± 18 bpm, p=0.64). Consistent with other models of GH and preeclampsia, the GH AGM had decreased offspring birthweight in comparison to NT offspring (352 ± 11 vs. 275 ± 12 g, p=0.01). Further, plasma osmolality of GH females was higher in late third trimester compared to NT females (286 ± 11 vs. 312 ± 9 mOsm, p=0.05). This higher plasma osmolality was associated with the GH female’s trend to higher AVP secretion as measured by copeptin (2 ± 2 vs. 4 ± 1 ng/g, p=0.280). In contrast to human pregnancies, late third trimester plasma [Na + ] of GH females was elevated compared to NT females (149 ± 3 vs. 157 ± 2 mMol/L, p=0.04). These data demonstrate that that the AGM model of preeclampsia replicates the plasma volume restricted findings consistent with human preeclampsia and possible insensitivity to control by AVP. Ongoing studies in early pregnancy will quantify changes in renal function during preeclampsia, differences in fluid volumes among NT and GH AGMs, and further the understanding of hormonal regulation of kidney function in the pathogenesis of preeclampsia in this translational AGM nonhuman primate.