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 Pierce; Katherine N Gibson-Corley; Curt D Sigmund; Mark K Santillan; Justin L Grobe

doi:10.1172/jci.insight.99403

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

Journal article

Open access

Peer reviewed

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, …

JCI insight, Vol.3(19), e99403

10/04/2018

DOI: 10.1172/jci.insight.99403

PMCID: PMC6237463

PMID: 30282823

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https://doi.org/10.1172/jci.insight.99403View

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Abstract

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in 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 expression consistent with human PE. Interestingly, these changes occurred despite a lack of placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1A receptor in the observed renal pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the blood pressure and fetal phenotypes. These findings demonstrate that AVP is sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVP may mechanistically (independently, and possibly synergistically with hypoxia) contribute to the development of clinical signs of PE in specific subtypes of human PE. Additionally, they identify divergent and gestational time-specific signaling mechanisms that mediate the development of PE phenotypes in response to AVP.

Pregnancy

Humans

Receptors, Vasopressin - metabolism

Neurophysins - administration & dosage

Vasopressins - metabolism

Vasopressins - administration & dosage

Neurophysins - metabolism

Antidiuretic Hormone Receptor Antagonists - administration & dosage

Female

Blood Pressure - drug effects

Blood Pressure Determination

Disease Models, Animal

Pre-Eclampsia - diagnosis

Recombinant Proteins - metabolism

Cell Hypoxia - drug effects

Protein Precursors - administration & dosage

Mice, Inbred C57BL

Pre-Eclampsia - etiology

Pre-Eclampsia - pathology

Recombinant Proteins - administration & dosage

Protein Precursors - metabolism

Placenta - drug effects

Animals

Placenta - pathology

Mice

Plethysmography

Details

Title: Subtitle: Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice
Creators: Jeremy A Sandgren - Department of Pharmacology
Guorui Deng - Department of Pharmacology
Danny W Linggonegoro - Department of Pharmacology
Sabrina M Scroggins - Department of Obstetrics & Gynecology
Katherine J Perschbacher - Department of Pharmacology
Anand R Nair - Department of Pharmacology
Taryn E Nishimura - Department of Obstetrics & Gynecology
Shao Yang Zhang - Department of Pharmacology
Larry N Agbor - Department of Pharmacology
Jing Wu
Henry L Keen - Department of Pharmacology
Meghan C Naber - Department of Pharmacology
Nicole A Pearson - Department of Pharmacology
Kathy A Zimmerman - Department of Internal Medicine
Robert M Weiss - Department of Internal Medicine
Noelle C Bowdler - Department of Obstetrics & Gynecology
Yuriy M Usachev - Department of Pharmacology
Donna A Santillan - University of Iowa Hospitals & Clinics Center for Hypertension Research
Matthew J Potthoff - Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA
Gary L Pierce - François M. Abboud Cardiovascular Research Center
Katherine N Gibson-Corley - Fraternal Order of Eagles' Diabetes Research Center, and
Curt D Sigmund - Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA
Mark K Santillan - University of Iowa Hospitals & Clinics Center for Hypertension Research
Justin L Grobe - Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA
Resource Type: Journal article
Publication Details: JCI insight, Vol.3(19), e99403
DOI: 10.1172/jci.insight.99403
PMID: 30282823
PMCID: PMC6237463
NLM abbreviation: JCI Insight
ISSN: 2379-3708
eISSN: 2379-3708
Publisher: United States
Grant note: S10 OD019941 / NIH HHS T32 GM067795 / NIGMS NIH HHS T32 AI007260 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS P01 HL084207 / NHLBI NIH HHS R01 HL134850 / NHLBI NIH HHS P30 CA086862 / NCI NIH HHS R01 NS087068 / NINDS NIH HHS
Language: English
Date published: 10/04/2018
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Anesthesia; Obstetrics and Gynecology; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine; Ophthalmology and Visual Sciences; Iowa Institute of Human Genetics
Record Identifier: 9983930274102771

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