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Angiotensin II responsiveness after preeclampsia: translational data from an experimental rat model and early-onset human preeclampsia

Item Type:Article
Title:Angiotensin II responsiveness after preeclampsia: translational data from an experimental rat model and early-onset human preeclampsia
Creators Name:van der Graaf, A.M. and Toering, T.J. and van der Wiel, M.W.K. and Frenay, A.R.S. and Wallukat, G. and Dechend, R. and Navis, G. and Groen, H. and Lely, A.T. and Faas, M.M.
Abstract:OBJECTIVE: Formerly preeclamptic women have an increased risk for cardiovascular and renal disease later in life. It is unknown which mechanisms contribute to this increased risk and whether this is induced by preeclampsia or by prepregnancy factors. We hypothesized that the increased risk for cardiovascular disease is partly due to an increased angiotensin II (ang II) responsiveness postpartum and that preeclampsia itself is involved in inducing this increased ang II responsiveness. METHODS: In never-pregnant, formerly healthy pregnant rats and rats with former experimental preeclampsia [experimental preeclampsia model induced by low-dose endotoxin infusion on day 14 of pregnancy; endotoxin-infused pregnant rats (EP-rats)], ang II responsiveness was studied by measuring changes in blood pressure (BP) and proteinuria after chronic ang II infusion with osmotic minipumps (200 ng/kg per min). In addition, we measured BP and responses to ang II (0.3, 1.0 and 3.0 ng/kg per min) in 18 formerly early-onset preeclamptic, without comorbidities, and 18 formerly healthy pregnant women (controls). RESULTS: In rats, a significantly higher systolic BP at termination was observed in formerly EP-rats vs. never-pregnant rats after ang II infusion (159.5 ± 29.5 vs. 136.7 ± 16.8; P = 0.049). In response to ang II, there was a significant increase in proteinuria in formerly EP-rats vs. healthy pregnant and never-pregnant rats (P < 0.01 for both). In humans, 1.0 ng/kg per min ang II showed a trend towards an increased mean arterial BP response in formerly preeclamptic women vs. controls (P = 0.057). CONCLUSION: Our data show an increased ang II responsiveness following (experimental) preeclampsia and support a role for preeclampsia itself in altered ang II responsiveness postpartum.
Keywords:Angiotensin II Responsiveness, Blood Pressure, Postpartum, Preeclampsia, Proteinuria, Rat Model, Animals, Rats
Source:Journal of Hypertension
ISSN:0263-6352
Publisher:Lippincott Williams & Wilkins
Volume:35
Number:12
Page Range:2468-2478
Date:December 2017
Official Publication:https://doi.org/10.1097/HJH.0000000000001474
PubMed:View item in PubMed

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