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Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.
JCI Insight 2018; 3(19)JI

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.

Authors+Show Affiliations

Department of Pharmacology.Department of Pharmacology.Department of Pharmacology.Department of Obstetrics & Gynecology.Department of Pharmacology.Department of Pharmacology.Department of Obstetrics & Gynecology.Department of Pharmacology.Department of Pharmacology.Department of Pharmacology.Department of Pharmacology.Department of Pharmacology.Department of Pharmacology.Department of Internal Medicine.Department of Internal Medicine.Department of Obstetrics & Gynecology.Department of Pharmacology.Department of Obstetrics & Gynecology. University of Iowa Hospitals & Clinics Center for Hypertension Research.Department of Pharmacology. University of Iowa Hospitals & Clinics Center for Hypertension Research. François M. Abboud Cardiovascular Research Center. Fraternal Order of Eagles' Diabetes Research Center, and. Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA.Department of Health & Human Physiology. University of Iowa Hospitals & Clinics Center for Hypertension Research. François M. Abboud Cardiovascular Research Center.Department of Pathology. University of Iowa Hospitals & Clinics Center for Hypertension Research. Fraternal Order of Eagles' Diabetes Research Center, and.Department of Pharmacology. University of Iowa Hospitals & Clinics Center for Hypertension Research. François M. Abboud Cardiovascular Research Center. Fraternal Order of Eagles' Diabetes Research Center, and. Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA.Department of Obstetrics & Gynecology. University of Iowa Hospitals & Clinics Center for Hypertension Research.Department of Pharmacology. University of Iowa Hospitals & Clinics Center for Hypertension Research. François M. Abboud Cardiovascular Research Center. Fraternal Order of Eagles' Diabetes Research Center, and. Obesity Research & Education Initiative, University of Iowa, Iowa City, Iowa USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30282823

Citation

Sandgren, Jeremy A., et al. "Arginine Vasopressin Infusion Is Sufficient to Model Clinical Features of Preeclampsia in Mice." JCI Insight, vol. 3, no. 19, 2018.
Sandgren JA, Deng G, Linggonegoro DW, et al. Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. JCI Insight. 2018;3(19).
Sandgren, J. A., Deng, G., Linggonegoro, D. W., Scroggins, S. M., Perschbacher, K. J., Nair, A. R., ... Grobe, J. L. (2018). Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. JCI Insight, 3(19), doi:10.1172/jci.insight.99403.
Sandgren JA, et al. Arginine Vasopressin Infusion Is Sufficient to Model Clinical Features of Preeclampsia in Mice. JCI Insight. 2018 10 4;3(19) PubMed PMID: 30282823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. AU - Sandgren,Jeremy A, AU - Deng,Guorui, AU - Linggonegoro,Danny W, AU - Scroggins,Sabrina M, AU - Perschbacher,Katherine J, AU - Nair,Anand R, AU - Nishimura,Taryn E, AU - Zhang,Shao Yang, AU - Agbor,Larry N, AU - Wu,Jing, AU - Keen,Henry L, AU - Naber,Meghan C, AU - Pearson,Nicole A, AU - Zimmerman,Kathy A, AU - Weiss,Robert M, AU - Bowdler,Noelle C, AU - Usachev,Yuriy M, AU - Santillan,Donna A, AU - Potthoff,Matthew J, AU - Pierce,Gary L, AU - Gibson-Corley,Katherine N, AU - Sigmund,Curt D, AU - Santillan,Mark K, AU - Grobe,Justin L, Y1 - 2018/10/04/ PY - 2017/12/20/received PY - 2018/08/17/accepted PY - 2018/10/5/entrez PY - 2018/10/5/pubmed PY - 2018/10/5/medline KW - Hypertension KW - Mouse models KW - Obstetrics/gynecology KW - Reproductive Biology JF - JCI insight JO - JCI Insight VL - 3 IS - 19 N2 - 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. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/30282823/Arginine_vasopressin_infusion_is_sufficient_to_model_clinical_features_of_preeclampsia_in_mice L2 - https://doi.org/10.1172/jci.insight.99403 DB - PRIME DP - Unbound Medicine ER -