Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. JCI Insight 2018 Oct 04;3(19)
Date
10/05/2018Pubmed ID
30282823Pubmed Central ID
PMC6237463DOI
10.1172/jci.insight.99403Scopus ID
2-s2.0-85063243804 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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.
Author List
Sandgren JA, Deng G, Linggonegoro DW, Scroggins SM, Perschbacher KJ, Nair AR, Nishimura TE, Zhang SY, Agbor LN, Wu J, Keen HL, Naber MC, Pearson NA, Zimmerman KA, Weiss RM, Bowdler NC, Usachev YM, Santillan DA, Potthoff MJ, Pierce GL, Gibson-Corley KN, Sigmund CD, Santillan MK, Grobe JLAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinCurt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntidiuretic Hormone Receptor Antagonists
Blood Pressure
Blood Pressure Determination
Cell Hypoxia
Disease Models, Animal
Female
Humans
Mice
Mice, Inbred C57BL
Neurophysins
Placenta
Plethysmography
Pre-Eclampsia
Pregnancy
Protein Precursors
Receptors, Vasopressin
Recombinant Proteins
Vasopressins