Journal article
Reductions in angiotensin II type 2 receptor-mediated vasodilation contribute to increased angiotensin II vasoconstrictor sensitivity in women with preeclampsia history
Clinical science (1979), Vol.139(11), pp.545-558
06/11/2025
DOI: 10.1042/CS20245238
PMCID: PMC12236177
PMID: 40411185
Appears in UI Libraries Support Open Access
Abstract
Women with a history of preeclampsia (hxPE) have a ≥4-fold risk for developing cardiovascular disease (CVD) compared with women who had a healthy pregnancy (hxHC). HxPE have exaggerated vasoconstrictor sensitivity to angiotensin (ang) II after pregnancy, which likely contributes to CVD progression after preeclampsia. Ang II-mediated constriction via ang II type 1 receptors (AT1R) is countered by vasodilatory ang II type 2 receptors (AT2R); however, the extent that reductions in AT2R-mediated responses contribute to exaggerated ang II-mediated constriction after preeclampsia is unknown. We examined the balance of AT1R- and AT2R-mediated responses in hxPE and hxHC (n=12/group). We hypothesized that 1) attenuated AT2R-mediated dilation would be improved with AT1R inhibition in hxPE, and 2) AT2R inhibition would increase ang II-mediated constriction in hxHC but have no effect in hxPE. We measured cutaneous vascular conductance responses to compound 21 (AT2R agonist; 10-14-10-8mol/L) alone or with losartan (AT1R antagonist; 43µmol/L) to assess AT2R-mediated dilation, and ang II (10-20-10-4mol/L) alone or with PD-123319 (AT2R antagonist; 1µmol/L) to assess the role of AT2R in vasoconstrictor sensitivity to ang II. Reduced AT2R-mediated dilation in hxPE (P=0.002) was improved with AT1R inhibition (P<0.001). Vasoconstrictor sensitivity to ang II was greater in hxPE compared with hxHC (P<0.001). Circulating AT1R agonistic autoantibodies (AT1-AA) were elevated in hxPE (P=0.015). AT2R inhibition increased the vasoconstrictor response to ang II in hxHC (P<0.001) but had no effect in hxPE (P=0.19). These data suggest that hxPE have reduced AT2R-mediated dilation that contributes to increased ang II vasoconstrictor sensitivity after preeclampsia.
Details
- Title: Subtitle
- Reductions in angiotensin II type 2 receptor-mediated vasodilation contribute to increased angiotensin II vasoconstrictor sensitivity in women with preeclampsia history
- Creators
- Kelsey Schwartz - University of IowaNathan Campbell - University of Mississippi Medical CenterDiana Jalal - University of IowaAnna Stanhewicz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical science (1979), Vol.139(11), pp.545-558
- DOI
- 10.1042/CS20245238
- PMID
- 40411185
- PMCID
- PMC12236177
- NLM abbreviation
- Clin Sci (Lond)
- ISSN
- 0143-5221
- eISSN
- 1470-8736
- Publisher
- Portland Press; LONDON
- Copyright
- © 2025 The Author(s)
- Grant note
- P20GM121334 / Mississippi Center for Excellence in Perinatal Research Graduate College Fellowship / The University of Iowa UM1TR004403 / NIH HHS
- Language
- English
- Electronic publication date
- 05/22/2025
- Date published
- 06/11/2025
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Nephrology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984825531602771
Metrics
6 Record Views