Abstract
Abstract 091: Chronic Vasopressin Infusion: A Novel, Clinically Significant, and Pregnancy-Specific Mouse Model of Preeclampsia
Hypertension (Dallas, Tex. 1979), Vol.64(suppl_1), pp.A091-A091
09/2014
DOI: 10.1161/hyp.64.suppl_1.091
Abstract
Recently we demonstrated that the late-pregnancy cardiovascular disorder, preeclampsia, is characterized by robust, early and sustained vasopressin (AVP) hypersecretion in all three trimesters of pregnancy in humans. We hypothesize a causative role for elevated AVP in the pathogenesis of preeclampsia. This concept was tested by chronically infusing AVP (0.24 - 240 ng/hr, s.c., or saline vehicle) in wildtype C57BL/6J female mice throughout pregnancy. In pregnant mice, AVP infusion caused
pregnancy-specific
increases in systolic blood pressure by tail-cuff plethysmography with significant increases in the pregnant cohort (saline n=16: 110±3, vs 24 ng/hr AVP n=11: 120±3 mmHg on GD15/16, P<0.05), but no significant difference in the nonpregnant cohort (saline n=14: 108±3, vs 24 ng/hr AVP n=5: 108±5 mmHg, P>0.05). In addition, the AVP infused mice exhibited increased proteinuria (0.24 ng/hr n=2: 66±73, 2.4 ng/hr n=5: 348±56, 24 ng/hr n=2: 799±297 mg/d, P<0.05), intrauterine growth restriction (saline n=25: 0.78±0.06, vs 24 ng/hr n=65: 0.55±0.03 g/fetus, P<0.05), spontaneous feto-placental unit resorption (saline: 0/65=0%, 0.24 ng/hr: 0/16=0%, 2.4 ng/hr: 2/45=4%, 24 ng/hr 8/73=11%, P<0.05), and maternal renal glomerular endotheliosis by electron microscopy. High doses of AVP reduced rates of successful pregnancy with single-night breeding (saline 8/18=44% vs 240 ng/hr 1/20=5%, P<0.05). These data demonstrate that AVP infusion - which simulates the large sustained increases in AVP secretion during human preeclampsia - is sufficient to induce all the cardinal phenotypes of preeclampsia in pregnant C57BL/6J mice. This identifies AVP infusion as a novel, clinically significant, and
pregnancy-specific
physiological model of preeclampsia in mice. These data support our hypothesis that AVP hypersecretion during pregnancy may be causative for the development of preeclampsia. Ongoing experiments are aimed at identifying the causes of AVP hypersecretion in human preeclampsia, the target tissues and receptors involved, and the utility of targeting AVP signaling as a novel therapeutic for preeclampsia.
Details
- Title: Subtitle
- Abstract 091: Chronic Vasopressin Infusion: A Novel, Clinically Significant, and Pregnancy-Specific Mouse Model of Preeclampsia
- Creators
- Mark Santillan - University of IowaDonna A Santillan - University of IowaSabrina M Scroggins - University of IowaJames Y Min - University of IowaJeremy A Sangren - University of IowaNicole A Pearson - University of IowaKatherine Gibson-Corley - University of IowaJustin L Grobe - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.64(suppl_1), pp.A091-A091
- DOI
- 10.1161/hyp.64.suppl_1.091
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Neuroscience and Pharmacology; Obstetrics and Gynecology; The University of Iowa Institute for Vision Research; Psychiatry
- Record Identifier
- 9984295043702771
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