Abstract
Abstract 12197: Increased Angiotensin II Sensitivity Contributes to Microvascular Endothelial Dysfunction in Women Who Have Had Preeclampsia
Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A12197-A12197
11/11/2016
Abstract
IntroductionWomen with a history of preeclampsia have increased cardiovascular disease risk, however the mechanisms responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist post-partum. The putative mechanisms mediating this dysfunction include a reduction in nitric oxide (NO)-dependent dilation, and an increased sensitivity to angiotensin II (ang II). In this study, we evaluated endothelium-dependent dilation, ang II sensitivity, and the therapeutic effect of ang II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (PrEC, n=7) and control women who had a healthy pregnancy (HC, n=9). We hypothesized that PrEC would have 1) reduced endothelium-dependent dilation, 2) reduced NO-mediated dilation, and 3) increased sensitivity to ang II. We further hypothesized that losartan would increase endothelium-dependent dilation in PrEC.MethodsWe assessed microvascular function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (ACh; 10-10M) and ang II (10-10M); and during ACh co-infusion with 15mM L-NAME (NO-synthase inhibitor) or 43μM losartan.ResultsACh-induced vasodilation was attenuated in PrEC compared to HC (PrEC -3.3±0.2 vs. HC -4.7±0.1 logEC50; p<0.05). There was no difference between PrEC and HC during ACh co-infusion with L-NAME (PrEC -4.4±0.2 vs. HC -4.6±0.2 logEC50; NS). NO-mediated dilation was attenuated in PrEC compared to HC (PrEC 10±4 vs. HC 35±4%; p<0.01). PrEC had a greater vasoconstriction response to ang II (PrEC -11.8±0.2 vs. HC -9.7±0.2 logEC50; p<0.05. Losartan co-infusion improved the vasodilation response to ACh in PrEC (losartan -4.6±0.2 vs. ACh alone -3.3±0.2 logEC50; NS).ConclusionsThese findings suggest that women who have had preeclampsia have impaired endothelium-dependent vasodilation which is mediated, in part, by reductions in NO signaling and increased sensitivity to ang II. Furthermore, losartan improved endothelium-dependent dilation, suggesting that ang II receptor blockade may have therapeutic potential to treat microvascular dysfunction in women who have had preeclampsia.
Details
- Title: Subtitle
- Abstract 12197: Increased Angiotensin II Sensitivity Contributes to Microvascular Endothelial Dysfunction in Women Who Have Had Preeclampsia
- Creators
- Anna Stanhewicz - Pennsylvania State UniversityLakshmi SanthanamLacy Alexander
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A12197-A12197
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/11/2016
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984267151702771
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