Abstract
Abstract 46: Reduced Angiotensin II Type 2 Receptor-Mediated Responses Contribute to Increased Angiotensin II Vasoconstrictor Sensitivity in Otherwise Healthy Women With a History Of Preeclampsia
Hypertension (Dallas, Tex. 1979), Vol.81(Suppl_1)
09/2024
DOI: 10.1161/hyp.81.suppl_1.46
Abstract
Abstract only Women with a history of preeclampsia (hxPE) have a ≥4-fold risk for developing cardiovascular disease compared to matched women who had a healthy pregnancy (hxHC). Angiotensin (ang) II-mediated vasoconstriction contributes to the persistently reduced microvascular function in the years after preeclampsia. Excessive activation of ang II type 1 receptors (AT 1 R) is one putative mechanism underlying increased ang II constrictor sensitivity. This may be countered by ang II type 2 receptor (AT 2 R) activation; however, the extent that reductions in AT 2 R-mediated responses contribute to increased ang II sensitivity after preeclampsia is unknown. Using the cutaneous microcirculation as a model, we hypothesized that 1) AT 2 R-mediated dilation is attenuated in hxPE compared with hxHC, 2) AT 1 R inhibition improves reduced AT 2 R-mediated dilation in hxPE, and 3) AT 2 R inhibition would increase ang II-mediated constriction in hxHC but have no effect in hxPE. Nine hxPE (37±5 years) and 9 matched hxHC (34±5 years) within 5 years postpartum had 4 intradermal microdialysis fibers placed in the ventral forearm for the local delivery of pharmacological agents. Two fibers received graded infusions of compound 21 (AT 2 R agonist; 10 -14 -10 -8 mol/L) alone or co-perfused with losartan (AT 1 R antagonist; 43µmol/L) for the assessment of AT 2 R-mediated dilation. The remaining 2 sites received graded infusions of ang II (10 −20 –10 −4 mol/L) alone or co-perfused with PD-123319 (AT 2 R antagonist; 1µmol/L) to assess the role of AT 2 R in vasoconstrictor sensitivity to ang II. Red blood cell flux was measured directly over each fiber and cutaneous vascular conductance was calculated (CVC=flux/MAP) and expressed as a % maximum (43°C + 28mM SNP) or % baseline. Those with hxPE had attenuated AT 2 R-mediated dilation (hxPE: 15±5 vs hxHC: 27±9%max; P=0.01) that was improved with AT 1 R inhibition (losartan: 22±7 vs control: 15±5%max; P=0.003). Vasoconstrictor sensitivity to ang II was greater in hxPE compared with hxHC (hxPE: 39±14 vs hxHC: 55±6%baseline; P<0.001). AT 2 R inhibition increased the vasoconstrictor response to ang II in hxHC (PD-123319: 39±12 vs control: 55±65%baseline; P<0.001) but had no effect in hxPE (PD-123319: 39±13 vs control: 39±14%baseline; P=0.29). These data suggest that women with a history of preeclampsia have reductions in AT 2 R-mediated dilation that contributes to increased ang II vasoconstrictor sensitivity and sustained microvascular dysfunction after preeclampsia.
Details
- Title: Subtitle
- Abstract 46: Reduced Angiotensin II Type 2 Receptor-Mediated Responses Contribute to Increased Angiotensin II Vasoconstrictor Sensitivity in Otherwise Healthy Women With a History Of Preeclampsia
- Creators
- Kelsey Schwartz - , Iowa City, Iowa, United StatesDiana Jalal - , Iowa City, Iowa, United StatesAnna Stanhewicz - , Iowa City, Iowa, United States
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.81(Suppl_1)
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- DOI
- 10.1161/hyp.81.suppl_1.46
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine; Nephrology
- Record Identifier
- 9984732541902771
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