Journal article
Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia
Hypertension (Dallas, Tex. 1979), Vol.70(2), pp.382-389
08/2017
DOI: 10.1161/HYPERTENSIONAHA.117.09386
PMCID: PMC5520653
PMID: 28652473
Abstract
Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10
-102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME (
-nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10
-10
mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log
;
<0.001) and NO-dependent dilation (16±3% versus 39±6%;
=0.006). Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5;
=0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum, mediated, in part, by increased sensitivity to angiotensin II.
Details
- Title: Subtitle
- Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia
- Creators
- Anna E Stanhewicz - Pennsylvania State UniversitySandeep Jandu - Johns Hopkins UniversityLakshmi Santhanam - Johns Hopkins MedicineLacy M Alexander - Johns Hopkins Medicine
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.70(2), pp.382-389
- DOI
- 10.1161/HYPERTENSIONAHA.117.09386
- PMID
- 28652473
- PMCID
- PMC5520653
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- F32 HL129677 / NHLBI NIH HHS R01 HL093238 / NHLBI NIH HHS
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259391502771
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