Abstract 577: Increased Uterine Interimplantation Levels of Ang II, AT1R, and CB1R are Associated with Reduced Uterine Permeability at Early Pregnancy in a Transgenic Model of Preeclampsia
Both the renin-angiotensin (RAS) and endocannabinoid (ECS) systems are down-regulated at the early stages of normal pregnancy. The striking similarity of the pattern of distribution of the two systems and their required down-regulation in early events of pregnancy make a compelling argument to compare their regulation in the early events of pregnancy in an animal that has placental activation of the RAS at late gestation. Female transgenic rats with overexpression of human (h) angiotensinogen were mated with male rats with h renin [Preeclamptic model (PRE)]. At day 7 of gestation, normal pregnant Sprague Dawley (SD) and PRE animals were anesthetized and bovine serum albumin (BSA) conjugated to Alexa Fluor 488 was injected systemically to assess uterine permeability in the implantation (IS) and interimplantation (IIS) uterine sites. Mean blood pressures were not different between SD and PRE animals (98.8±2 vs 97±3 mmHg, p>0.05). Uterine permeability measured as the IS/IIS ratio of fluorescent BSA signal was decreased in PRE vs. SD (1.36±0.2 vs 0.68±0.1, p<0.05). The levels of Ang II and AT1R mRNA were increased in the IIS of PRE vs IS of PRE and IIS of SD (FIGURE). CB1R mRNA was increased in the IIS vs. IS of PRE rats, and this was associated with a significant increase in the levels of total 1+2-arachidonoylglycerol (24.9±4.1 vs 12.2±3.5 ng/mg protein, p<0.05) in IIS of PRE vs IIS of SD. These data demonstrate a synergistic up-regulation of the RAS and ECS associated with reduced uterine permeability at early pregnancy in a PRE model. These changes precede the hypertensive phenotype and are consistent with a critical role for the disrupted RAS and alterations in the ECS in early pregnancy.
Author Disclosures: K. Brosnihan: None. V.M. Pulgar: None. J. Varagic: None. K. Oliva: None. M. Bader: None. R. Dechend: None. P. Gallagher: None. B.F. Thomas: None. M. Grabenauer: None. L.M. Yamaleyeva: None.
- © 2014 by American Heart Association, Inc.