Local angiotensin-(1–7) administration improves microvascular endothelial function in women who have had preeclampsia

Anna E. Stanhewicz, Lacy M. Alexander

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11 Scopus citations

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 druggable 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 102 mmol/L) in control sites and sites treated with 15 mmol/L NG-nitroL-arginine methyl ester (L-NAME; NO-synthase inhibitor), 100 μmol/L Ang-(1–7), or 15 mmol/L L-NAME + 100 μmol/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 μmol/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.

Original languageEnglish (US)
Pages (from-to)R148-R155
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume318
Issue number1
DOIs
StatePublished - Jan 2020

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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