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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., Brosnihan, K.B., Elsangeedy, E., McGee, C., Shi, S., Caudell, D., Miller, C., Varagic, J., Bader, M., 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 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 1 |
| 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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