Vasopressin in Preeclampsia

Abstract

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. As other non-pregnant low-renin hypertensive disorders often exhibit and are occasionally dependent upon elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert pro-segment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life than AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, BMI, chronic essential hypertension, twin gestation, diabetes, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the 6th week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng/hr) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data (1) implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, (2) identify chronic AVP infusion as a novel and clinically-relevant model of preeclampsia in mice, and are (3) consistent with a potential causative role for AVP in preeclampsia in humans.

Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings

“…Three new blood biomarkers [glycosylated fibronectin (GlyFN) [57], transthyretin [58] and vasopressin [59]], and two new urine biomarkers (urine congophilia [60] and urinary adipsin [61]) were identified, which added to our preexisting list of experimental biomarkers (Figure 1). A total of 11 promising single experimental blood and seven urine biomarkers together with the four established markers were ranked according to the following criteria: 1) characteristics related to performance; and 2) other characteristics such as whether a kit or commercial antibodies exist (Table 2A and 2B).…”

“…Vasopressin, though not a candidate meeting "good" criteria, is still worth mentioning. Santillan et al showed that maternal plasma vasopressin concentration is predictive of the development of PE in all three trimesters with clinically significant sensitivities ranging from 78% to 88% and specificities ranging from 71% to 84% [59].…”

The role of hyponatremia in preeclampsia

“…Before this, a mechanism had been proposed that related to oxytocin, vasopressin and their products were raised by premature contractions and preterm labor [22]. Furthermore, increased vasopressin levels are in doubt about preeclampsia as other low-renin hypertensive states and copeptin has been reported which is surrogate of vasopressin is an useful biomarker for the prediction of preeclampsia [28]. It highlights the role of hyponatremia in preeclampsia that is severity.…”

Low Plasma Volume in Normotensive Formerly Preeclamptic Women Predisposes to Hypertension

“…Recent studies have suggested a pathophysiological role of increased vasopressin levels in preeclampsia. 21 If vasopressin increases, one would expect higher PV levels unless the vasopressin is increased secondary to LPV status. In pregnancy, however, women who develop preeclampsia are not chronically underfilled because compensatory neurohumoral changes such as elevated renin, angiotensin, and aldosterone levels are lacking.…”