Systemic Outcomes of (Pyr 1)-Apelin-13 Infusion at Mid-Late Pregnancy in a Rat Model with Preeclamptic Features

Sci Rep. 2019 Jun 12;9(1):8579. doi: 10.1038/s41598-019-44971-0.

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Animals
  • Disease Models, Animal
  • Female
  • Hemodynamics / drug effects*
  • Hemodynamics / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic

Substances

  • AGT protein, human
  • Intercellular Signaling Peptides and Proteins
  • apelin 13, Pyr(1)-
  • Angiotensinogen