Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats - role of endothelin-1

Tools

Item Type:	Article
Title:	Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats - role of endothelin-1
Creators Name:	Lamarca, B., Parrish, M., Ray, L.F., Murphy, S.R., Roberts, L., Glover, P., Wallukat, G., Wenzel, K., Cockrell, K., Martin, J.N., Ryan, M.J. and Dechend, R.
Abstract:	Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and endothelin -1 (ET-1) are suggested to be important links between placental ischemia and hypertension during preeclampsia. Activation of the angiotensin II type 1 receptor (AT1R) increases endothelial cell production of ET-1; however, the importance of ET-1 in response to AT1-AA-mediated AT1 R activation during preeclampsia is unknown. Furthermore, the role of AT1-AA-mediated increases in blood pressure during pregnancy remains unclear. The objective of this study was to test the hypothesis that AT1-AA, increased to levels observed in preeclamptic women and placental ischemic rats, increases mean arterial pressure (MAP) by activation of the ET-1 system. Chronic infusion of purified rat AT1-AA into normal pregnant (NP) rats for 7 days increased AT1-AA from 0.68+/-0.5 to 10.88+/-1.1 chronotropic units (P<0.001). The increased AT1-AA increased MAP from 99+/-1 to 119+/-2 mm Hg (P<0.001). The hypertension was associated with significant increases in renal cortices (11-fold) and placental (4-fold) ET-1. To determine whether ET-1 mediates AT1-AA-induced hypertension, pregnant rats infused with AT1-AA and NP rats were treated with an ETA receptor antagonist. MAP was 100+/-1 mm Hg in AT1-AA+ETA antagonist-treated rats versus 98+/-2 mm Hg in ETA antagonist-treated rats. Collectively, these data support the hypothesis that one potential pathway whereby AT1-AAs increase blood pressure during pregnancy is by an ET-1-dependent mechanism.
Keywords:	Preeclampsia, Hypertension, Kidney, Placenta, Inflammation, Animals, Rats
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	54
Number:	4
Page Range:	905-909
Date:	October 2009
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.109.137935
PubMed:	View item in PubMed

Repository Staff Only: item control page