Abstract 126: Systemic Administration of (Pyr1)-Apelin-13 at Late Pregnancy Reduces Blood Pressure, Proteinuria, and Improves Autonomic Function in Preeclamptic Rats
Preeclampsia is associated with maternal perinatal morbidity and mortality and a high risk of premature birth and intrauterine growth restriction. The apelin system is a novel pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We have previously reported that total apelin content is lower in human preeclamptic chorionic villi. In this study, we determined whether (Pyr1)-apelin-13 improves hypertension, proteinuria, fetal characteristics, uteroplacental hemodynamics, and the autonomic function in preeclamptic rats (TgA, female transgenic for human angiotensinogen mated to male transgenic for human renin). (Pyr1)-apelin-13 (2 mg/kg/day) (n=7) or saline (n=5) was infused in TgA via osmotic minipumps starting at day 13 of gestation, when blood pressure begins to increase in these animals. Pregnant SD (n=6) rats were used as controls. At the 20th day of pregnancy, TgA rats had higher MAP (138±6 vs. 79±3 mmHg in SD, p<0.001) which was reduced by (Pyr1)-apelin treatment to 119±2 mmHg vs. TgA, p<0.006. TgA rats also had impaired heart rate variability measured as root of mean successive differences (rMSSD) compared with SD (2.7±0.4 vs. 3.8±0.3 ms in SD, p<0.05). Apelin treatment normalized rMSSD to 3.6±0.3, p<0.05. Similarly, baroreflex sensitivity measured in the sequence domain was lower in TgA (0.7±0.1 vs. 2.6±0.5 ms/mmHg in SD, p<0.01) and normalized with (Pyr1)-apelin-13 to 2.0 ± 0.4 ms/mmHg, p<0.05. Proteinuria was greater in TgA (53±9 vs. 10±2 mg/kg/day, p<0.001), and normalized by (Pyr1)-apelin-13 (18±6, p<0.05). Pup (3.0±0.1 vs. 3.7±0.1 g, p<0.01) and placental weight (0.41±0.01 vs. 0.45±0.01 g, p<0.01), and pup number (10.7±1.1 vs. 14.0±0.8, p<0.01) were lower in TgA vs. SD; however they were not changed by (Pyr1)-apelin-13. Uterine artery peak systolic velocity was not different between SD and TgA, but increased with (Pyr1)-apelin-13 treatment (179.5±16.7 vs. 122.6±16.7 ml/min, p<0.05) with no change in resistance index. In conclusion, our findings suggest that (Pyr1)-apelin-13 may be beneficial for the treatment of preeclampsia due to its hemodynamic and renoprotective effects. We also report for the first time that these changes may involve central control of the cardiovascular system.
Author Disclosures: L.M. Yamaleyeva: None. K. Brosnihan: None. C. McGee: None. S. Shi: None. J. Varagic: None. M. Bader: None. R. Dechend: None. H.A. Shaltout: None.
- © 2015 by American Heart Association, Inc.