Abstract
Abstract P262: Vasopressin Receptors Regulate Immune Responses in Preeclampsia
Hypertension (Dallas, Tex. 1979), Vol.70(suppl_1)
09/2017
DOI: 10.1161/hyp.70.suppl_1.p262
Abstract
The pathogenesis of preeclampsia (PE) involves imbalanced T helper (T
H
) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated secretion of arginine vasopressin (AVP) precedes the development of symptoms in PE in humans, and chronic infusion of AVP (24 ng/hr s.c.) throughout gestation is sufficient to initiate cardiovascular, renal, and immune phenotypes of PE in wild-type C57BL/6J mice.
We hypothesize that increased AVP signaling may mediate the immune changes observed in PE.
AVP infusion throughout gestation in mice resulted in increased pro-inflammatory IFNγ (T
H
1) in the maternal plasma (N=7, p<0.05) and IL-17 (T
H
17) in the placenta (N≥10, p<0.001). The T
H
2-associated anti-inflammatory cytokines IL-4 and IL-10 were decreased in maternal kidney (IL-4: N=8, p<0.05; IL-10: N=5, p<0.01) and fetal kidney (IL-4: N=5, p<0.05; IL-10: N=5, p<0.05) of AVP-infused dams.
To elucidate the receptor dependency of these effects,
AVP-infused dams were simultaneously treated with chronic infusion of AVP V
1A
and/or V
2
receptor antagonists (22 ng/hr s.c). Combined blockade of V
1a
+V
2
receptors by conivaptan, as well as specifically blocking V
2
by tolvaptan, corrected AVP induced reductions in IL-4 in maternal (conivaptan: N=5, p<0.05; tolvaptan: N=5, p<0.0.0001) and fetal kidneys (conivaptan: N=5, p<0.0001; tolvaptan: N=5, p<0.05). These data implicate V
2
as the receptor involved in kidney IL-4 deficiency in PE, whereby blockade of V
2
restores IL-4, preventing inflammation. Combined blockade of V
1A
+V
2
receptors by conivaptan corrected the placental loss of IL-4 (N=5, p<0.05), whereas blockade of either receptor alone was insufficient, suggesting loss of placental IL-4 via AVP is mediated by both V
1a
and V
2
receptors. In contrast, increased placental IL-17 was only corrected by selective blockade of V
1A
by relcovaptan (N=5, p<0.05), suggesting a novel role for V1a receptor in pro-inflammatory placental IL-17 production in PE. Collectively these results demonstrate the sufficiency of AVP to induce the immune changes typical of PE, and support a dominant role for V
1A
in the induction of pro-inflammatory IL-17 (T
H
17) release versus a dominant role for V
2
receptors in the suppression of anti-inflammatory IL-4 (T
H
2) release.
Details
- Title: Subtitle
- Abstract P262: Vasopressin Receptors Regulate Immune Responses in Preeclampsia
- Creators
- Sabrina M Scroggins - University of IowaDonna A Santillan - University of IowaDaffney T Gomendoza - University of IowaLindsay K Gravatt - University of IowaKathryn J Huber-Keener - University of IowaKatherine J Perschbacher - University of IowaJeremy A Sandgren - University of IowaEric J Devor - University of IowaJustin L Grobe - University of IowaMark K Santillan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.70(suppl_1)
- DOI
- 10.1161/hyp.70.suppl_1.p262
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984316901002771
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