Systemic Outcomes of (Pyr1)-Apelin-13 Infusion at Mid-Late Pregnancy in a Rat Model with Preeclamptic Features

Autor: Ebrahim Elsangeedy, Sara Shi, Carolynne McGee, David L. Caudell, Hossam A. Shaltout, Liliya M. Yamaleyeva, Ralf Dechend, Cynthia Miller, K. Bridget Brosnihan, Michael Bader, Jasmina Varagic
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-44971-0
Popis: 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 (Pyr1)-apelin-13 administration in rats with preeclamptic features (TGA-PE, female transgenic for human angiotensinogen mated to male transgenic for human renin). (Pyr1)-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). (Pyr1)-apelin-13 did not affect maternal or fetal weights in TGA-PE. The administration of (Pyr1)-apelin-13 reduced blood pressure, and normalized heart rate variability and baroreflex sensitivity in TGA-PE rats compared to controls. (Pyr1)-apelin-13 increased ejection fraction in TGA-PE rats. (Pyr1)-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.
Databáze: OpenAIRE
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