The objective of this research is to define the mechanisms mediating pregnancy induced hypertension. The central hypothesis to be tested in this proposal is that a reduction in uteroplacental perfusion pressure causes hypertension by reducing renal-pressure natriuresis. The reduction in pressure natriuresis occurs as a result of placental and/or leukocyte-derived cytokines causing endothelial cell activation that leads to enhanced formation of endothelin. These abnormalities reduced renal plasma flow and glomerular filtration thereby decreasing renal sodium excretory function. To test this hypothesis, arterial pressure, renal, hormonal, and endothelial function will be examined in a conscious, chronically-instrumented rat model of chronic PIH produced by long-term reductions in uterine perfusion pressure (RUPP). In addition, in vitro studies utilizing endothelial cell culture will be used to determine the interaction between inflammatory cytokines, sex steroids and endothelin production.
Specific aims to be addressed are: 1) To test the hypothesis that abnormalities in cardiovascular and renal function during chronic reductions in uteroplacental perfusion pressure are due to elevations in maternal plasma levels of inflammatory cytokines such as TNF alpha and IL-6; 2) To test the hypothesis that estrogens and/or progesterone enhance the endothelial activation and hypertensive response to TNF alpha and IL-6 .
| Shekhar, Shashank; Cunningham, Mark W; Pabbidi, Mallikarjuna R et al. (2018) Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches. Eur J Pharmacol 833:531-544 |
| Faulkner, Jessica L; Plenty, Nicole L; Wallace, Kedra et al. (2018) Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia. Prostaglandins Other Lipid Mediat 134:108-113 |
| Cunningham Jr, Mark W; Castillo, Javier; Ibrahim, Tarek et al. (2018) AT1-AA (Angiotensin II Type 1 Receptor Agonistic Autoantibody) Blockade Prevents Preeclamptic Symptoms in Placental Ischemic Rats. Hypertension 71:886-893 |
| Ibrahim, Tarek; Przybyl, Lukasz; Harmon, Ashlyn C et al. (2017) Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy. Am J Reprod Immunol 78: |
| Cunningham Jr, Mark W; Williams, Jan M; Amaral, Lorena et al. (2016) Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance Angiotensin II-Induced Renal Vascular Sensitivity and Reduce Renal Function During Pregnancy. Hypertension 68:1308-1313 |
| Faulkner, Jessica L; Cornelius, Denise C; Amaral, Lorena M et al. (2016) Vitamin D supplementation improves pathophysiology in a rat model of preeclampsia. Am J Physiol Regul Integr Comp Physiol 310:R346-54 |
| Harmon, Ashlyn C; Cornelius, Denise C; Amaral, Lorena M et al. (2016) The role of inflammation in the pathology of preeclampsia. Clin Sci (Lond) 130:409-19 |
| LaMarca, Babbette; Amaral, Lorena M; Harmon, Ashlyn C et al. (2016) Placental Ischemia and Resultant Phenotype in Animal Models of Preeclampsia. Curr Hypertens Rep 18:38 |
| Harmon, Ashlyn; Cornelius, Denise; Amaral, Lorena et al. (2015) IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat model of preeclampsia. Hypertens Pregnancy 34:291-306 |
| Amaral, Lorena M; Cunningham Jr, Mark W; Cornelius, Denise C et al. (2015) Preeclampsia: long-term consequences for vascular health. Vasc Health Risk Manag 11:403-15 |
Showing the most recent 10 out of 41 publications
