Journal article
Reduced AT 2 R Signaling Contributes to Endothelial Dysfunction After Preeclampsia
Hypertension (Dallas, Tex. 1979), Vol.82(5), pp.904-913
05/2025
DOI: 10.1161/HYPERTENSIONAHA.124.24098
PMCID: PMC12003086
PMID: 39723536
Abstract
BACKGROUND:
Women who had preeclampsia (a history of preeclampsia) have a >4-fold risk of developing cardiovascular disease compared with women who had an uncomplicated pregnancy (history of healthy pregnancy). Despite the remission of clinical symptoms after pregnancy, vascular endothelial dysfunction persists postpartum, mediated in part by exaggerated Ang II (angiotensin II)–mediated constriction. However, the role of vasodilatory AT2Rs (Ang II type 2 receptors) in this dysfunction is unknown. We examined the functional role of AT2R in the microvasculature postpartum and whether acute activation of AT2R improves microvascular endothelial function after preeclampsia.
METHODS:
Overall, 24 women (n=12/group) participated. We measured cutaneous vascular conductance responses to (1) graded infusion of compound 21 (AT2R agonist; 10−14–10−8M) alone or with NG-nitro-l-arginine methyl ester (NO synthase inhibitor; 15 mM) and (2) a standardized local heating protocol in control and 10−11M compound 21–treated sites. Expression of Ang II receptor subtypes I and II in biopsied venous endothelial cells was quantified using immunofluorescence.
RESULTS:
AT2R-mediated dilation (P<0.01) and the NO-dependent contribution (P=0.003) of this response were reduced in women with a history of preeclampsia. Endothelial AT2R expression was lower in women with a history of preeclampsia (P<0.01), but there were no differences in endothelial AT1R (Ang II type 1 receptor) expression (P>0.05). Acute activation of AT2R during local heating improved endothelium (P<0.01) and NO-dependent (P<0.01) dilation in women with a history of preeclampsia but had no effect in women with a history of healthy pregnancy (both P>0.05).
CONCLUSIONS:
Reductions in AT2R-mediated dilation contribute to attenuated or impaired endothelial function in women who had a pregnancy complicated by preeclampsia. Furthermore, AT2R activation may improve endothelial function through NO-dependent mechanisms in otherwise healthy women who had preeclampsia before the onset of cardiovascular disease.
Details
- Title: Subtitle
- Reduced AT 2 R Signaling Contributes to Endothelial Dysfunction After Preeclampsia
- Creators
- Kelsey S Schwartz - University of IowaMingyao Sun - Department of Internal Medicine, Carver College of Medicine, Iowa City, IA. (M.S., D.I.J.)Diana I Jalal - Department of Internal Medicine, Carver College of Medicine, Iowa City, IA. (M.S., D.I.J.)Mark K Santillan - University of IowaAnna E Stanhewicz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.82(5), pp.904-913
- DOI
- 10.1161/HYPERTENSIONAHA.124.24098
- PMID
- 39723536
- PMCID
- PMC12003086
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Publisher
- American Heart Association
- Grant note
- National Institutes of Health (NI H) Clinical and Translational Science Award: UM1TR0044 03
This project was supported in part by the National Institutes of Health (NI H) Clinical and Translational Science Award UM1TR0044 03 (University of Iowa Institute for Clinical and Translational Science).
- Language
- English
- Electronic publication date
- 12/26/2024
- Date published
- 05/2025
- Academic Unit
- Obstetrics and Gynecology; Fraternal Order of Eagles Diabetes Research Center; Nephrology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984769630102771
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