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Systemic outcomes of (Pyr(1))-apelin-13 infusion at mid-late pregnancy in a rat model with preeclamptic features

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Item Type:Article
Title:Systemic outcomes of (Pyr(1))-apelin-13 infusion at mid-late pregnancy in a rat model with preeclamptic features
Creators Name:Yamaleyeva, L.M. and Brosnihan, K.B. and Elsangeedy, E. and McGee, C. and Shi, S. and Caudell, D. and Miller, C. and Varagic, J. and Bader, M. and Dechend, R. and Shaltout, H.A.
Abstract:Preeclampsia is a syndrome with diverse clinical presentation that currently has no cure. The apelin receptor system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We established the systemic outcomes of (Pyr(1))-apelin-13 administration in rats with preeclamptic features (TGA-PE, female transgenic for human angiotensinogen mated to male transgenic for human renin). (Pyr(1))-apelin-13 (2 mg/kg/day) or saline was infused in TGA-PE rats via osmotic minipumps starting at day 13 of gestation (GD). At GD20, TGA-PE rats had higher blood pressure, proteinuria, lower maternal and pup weights, lower pup number, renal injury, and a larger heart compared to a control group (pregnant Sprague-Dawley rats administered vehicle). (Pyr(1))-apelin-13 did not affect maternal or fetal weights in TGA-PE. The administration of (Pyr(1))-apelin-13 reduced blood pressure, and normalized heart rate variability and baroreflex sensitivity in TGA-PE rats compared to controls. (Pyr(1))-apelin-13 increased ejection fraction in TGA-PE rats. (Pyr(1))-apelin-13 normalized proteinuria in association with lower renal cortical collagen deposition, improved renal pathology and lower immunostaining of oxidative stress markers (4-HNE and NOX-4) in TGA-PE. This study demonstrates improved hemodynamic responses and renal injury without fetal toxicity following apelin administration suggesting a role for apelin in the regulation of maternal outcomes in preeclampsia.
Keywords:Angiotensinogen, Animal Disease Models, Hemodynamics, Intercellular Signaling Peptides and Proteins, Oxidative Stress, Pre-Eclampsia, Pregnancy, Sprague-Dawley Rats, Transgenic Rats, Animals, Rats
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:8579
Date:12 June 2019
Official Publication:https://doi.org/10.1038/s41598-019-44971-0
PubMed:View item in PubMed

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