Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

Anna E. Stanhewicz, Sandeep Jandu, Lakshmi Santhanam, Lacy Marie Alexander

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME (N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 μmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50; P<0.001) and NO-dependent dilation (16±3% versus 39±6%; P=0.006). Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P=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.

Original languageEnglish (US)
Pages (from-to)382-389
Number of pages8
JournalHypertension
Volume70
Issue number2
DOIs
StatePublished - Aug 1 2017

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Pre-Eclampsia
Angiotensin II
Dilatation
Endothelium
Losartan
Angiotensin Receptors
Vasoconstrictor Agents
Vasodilation
Pregnancy
Postpartum Period
Acetylcholine
Endothelium-Dependent Relaxing Factors
Angiotensin I
NG-Nitroarginine Methyl Ester
Therapeutic Uses
Microvessels
Nitric Oxide Synthase
Heating
Blood Vessels
Cardiovascular Diseases

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Stanhewicz, Anna E. ; Jandu, Sandeep ; Santhanam, Lakshmi ; Alexander, Lacy Marie. / Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia. In: Hypertension. 2017 ; Vol. 70, No. 2. pp. 382-389.
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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 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME (N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 μmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50; P<0.001) and NO-dependent dilation (16±3{\%} versus 39±6{\%}; P=0.006). Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P=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.",
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Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia. / Stanhewicz, Anna E.; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy Marie.

In: Hypertension, Vol. 70, No. 2, 01.08.2017, p. 382-389.

Research output: Contribution to journalArticle

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