Journal article
Local angiotensin-(1-7) administration improves microvascular endothelial function in women who have had preeclampsia
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(1), pp.R148-R155
01/01/2020
DOI: 10.1152/ajpregu.00221.2019
PMCID: PMC6985799
PMID: 31577152
Abstract
Despite remission of clinical symptoms postpartum, women who have had preeclampsia demonstrate microvascular endothelial dysfunction, mediated in part by increased sensitivity to angiotensin II (ANG II). Angiotensin-(1-7) [Ang-(1-7)] is an endogenous inhibitor of the actions of ANG II and plausible drug-gable target in women who had preeclampsia. We therefore examined the therapeutic potential of Ang-(1-7) in the microvasculature of women with a history of preeclampsia (PrEC; n = 13) and parity-matched healthy control women (HC; n = 13) hypothesizing that administration of Ang-(1-7) would increase endothelium-dependent dilation and nitric oxide (NO)-dependent dilation and decrease ANG II-mediated constriction in PrEC. Using the cutaneous microcirculation, we assessed endothelium-dependent vasodilator function in response to graded infusion of acetylcholine (ACh; 10(-7) to 10(2) mmol/L) in control sites and sites treated with 15 mmol/L N-G-nitro-L-arginine methyl ester (L-NAME; NO-synthase inhibitor), 100 mu mol/L Ang-(1-7), or 15 mmol/L L-NAME + 100 mu mol/L Ang-(1-7). Vasoconstrictor function was measured in response to ANG II (10(-20)-10(-4) mol/L) in control sites and sites treated with 100 mu mol/L Ang-(1-7). PrEC had reduced endothelium-dependent dilation (P < 0.001) and NO-dependent dilation (P = 0.04 vs. HC). Ang-(1-7) coinfusion augmented endothelium-dependent dilation (P < 0.01) and NO-dependent dilation (P = 0.03) in PrEC but had no effect in HC. PrEC demonstrated augmented vasoconstrictor responses to ANG II (P < 0.01 vs. HC), which was attenuated by coinfusion of Ang-(1-7) (P < 0.001). Ang-(1-7) increased endothelium-dependent vasodilation via NO synthase-mediated pathways and attenuated ANG II-mediated constriction in women who have had preeclampsia, suggesting that Ang-(1-7) may be a viable therapeutic target for improved microvascular function in women who have had a preeclamptic pregnancy.
Details
- Title: Subtitle
- Local angiotensin-(1-7) administration improves microvascular endothelial function in women who have had preeclampsia
- Creators
- Anna E. Stanhewicz - Pennsylvania State UniversityLacy M. Alexander - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(1), pp.R148-R155
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajpregu.00221.2019
- PMID
- 31577152
- PMCID
- PMC6985799
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Number of pages
- 8
- Grant note
- HL-129677-03; HL-138133-01; HL-093238-07 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 01/01/2020
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259645702771
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