Local Angiotensin 1–7 Administration Augments Microvascular Endothelial Function in Women Who Have Had Preeclampsia

Anna Stanhewicz; Lacy Alexander

doi:10.1096/fasebj.2018.32.1_supplement.845.1

Women with a history of preeclampsia are at increased risk of developing cardiovascular disease. Despite remission of the clinical symptoms of preeclampsia postpartum, women who have had preeclampsia demonstrate microvascular endothelial dysfunction, mediated in part by increased sensitivity to angiotensin II. Angiotensin 1–7 (ang 1–7) is an endogenous inhibitor of the actions of angiotensin II and therefore a biologically plausible target for improving endothelial function in postpartum women who have had preeclampsia. Using the cutaneous microcirculation as a model, we hypothesized that women who have had preeclampsia (PreEC) would have attenuated endothelium‐dependent‐ and reduced nitric oxide (NO)‐dependent vasodilation compared to control women who had a normal pregnancy (HC). We further hypothesized that localized ang 1–7 administration would increase endothelium‐dependent vasodilation and NO‐dependent vasodilation in PreEC, but not HC. The subject sample included 8 PreEC (26±2 yrs of age; 6±2 months post‐partum) and 7 HC (32±2 yrs; 6±1 months post‐partum). Four intradermal microdialysis fibers were placed in the skin of the ventral forearm for the graded infusion of acetylcholine (ACh, 10−7 – 102 mM), ACh + 15 mM NG Nitro‐L‐arginine methyl ester (L‐NAME; nitric oxide synthase antagonist), ACh + 100μM ang 1–7, or ACh + 15 mM L‐NAME + 100μM ang 1–7. Red cell flux was measured over each site by laser‐Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC=LDF/MAP) and normalized to the respective site‐specific maximum (%CVCmax; 28 mM SNP + local heating to 43°C). ACh‐induced vasodilation was attenuated in PreEC compared to HC (logEC50: −1.0±0.2 vs. −1.8±0.1; p=0.04). There was no difference between PreEC and HC when ACh was co‐infused with L‐NAME (PreEC logEC50: −0.9±0.3 vs. HC: −1.2±0.2 logEC50). ACh + Ang 1–7 co‐infusion augmented the vasodilation response in PreEC (logEC50: −1.9±0.1) compared to ACh alone (logEC50: −1.0±0.2) (p<0.001) but had no effect in HC. Co‐infusion of ang1–7 + L‐NAME + ACh did not differ from ACh + L‐NAME in either group. Women who have had preeclampsia demonstrate attenuated endothelium‐dependent and NO‐dependent vasodilation compared to women who have had a healthy pregnancy. Ang 1–7 increased endothelium‐dependent vasodilation via NOS‐mediated pathways in women who have had preeclampsia, suggesting that ang 1–7 may be a viable therapeutic target for improved microvascular endothelial function in women who have had a preeclamptic pregnancy. Support or Funding Information NIH F32 HL129677‐03 (Stanhewicz), R01 HL093238‐07 (Alexander) This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.

Local Angiotensin 1–7 Administration Augments Microvascular Endothelial Function in Women Who Have Had Preeclampsia

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