Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice

Jeremy A. Sandgren, Guorui Deng, Danny W. Linggonegoro, Sabrina M. Scroggins, Katherine J. Perschbacher, Anand R. Nair, Taryn E. Nishimura, Shao Yang Zhang, Larry N. Agbor, Jing Wu, Henry L. Keen, Meghan C. Naber, Nicole A. Pearson, Kathy A. Zimmerman, Robert M. Weiss, Noelle C. Bowdler, Yuriy M. Usachev, Donna A. Santillan, Matthew J. Potthoff, Gary L. PierceKatherine N. Gibson-Corley, Curt D. Sigmund, Mark K. Santillan, Justin L. Grobe

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout humanpregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation issufcient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVPin the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension,renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor(PGF), altered placental morphology, placental oxidative stress, and placental gene expressionconsistent with human PE. Interestingly, these changes occurred despite a lack of placentalhypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptorantagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1Areceptor in the observed renal pathologies, versus mid-and late-gestational roles for the AVPR2receptor in the blood pressure and fetal phenotypes. These fndings demonstrate that AVP issufcient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVPmay mechanistically (independently, and possibly synergistically with hypoxia) contribute to thedevelopment of clinical signs of PE in specifc subtypes of human PE. Additionally, they identifydivergent and gestational time-specifc signaling mechanisms that mediate the development ofPE phenotypes in response to AVP.

Original languageEnglish (US)
Article numbere99403
JournalJCI Insight
Volume3
Issue number19
DOIs
StatePublished - Oct 4 2018
Externally publishedYes

Bibliographical note

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© 2018 American Society for Clinical Investigation. All rights reserved.

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