Acute systemic inhibition of inflammation augments endothelium-dependent dilation in women with a history of preeclamptic pregnancy

Anna E Stanhewicz; Gabrielle A Dillon; Corinna Serviente; Lacy M Alexander

doi:10.1016/j.preghy.2021.12.010

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Journal article

Acute systemic inhibition of inflammation augments endothelium-dependent dilation in women with a history of preeclamptic pregnancy

Anna E Stanhewicz, Gabrielle A Dillon, Corinna Serviente and Lacy M Alexander

Pregnancy hypertension, Vol.27, pp.81-86

03/2022

DOI: 10.1016/j.preghy.2021.12.010

PMCID: PMC8858855

PMID: 34973597

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https://www.ncbi.nlm.nih.gov/pmc/articles/8858855View

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Abstract

Women who have had preeclampsia demonstrate microvascular endothelial-dysfunction, mediated in part by reduced nitric oxide (NO)-dependent dilation. Preeclamptic pregnancies are associated with elevated inflammation, and inhibition of inflammation attenuates endothelial damage in animal models of preeclampsia. However, it is unclear if inhibition of vascular inflammation improves endothelial function in women after a preeclamptic pregnancy. Using the cutaneous microcirculation as a model, we hypothesized that acute systemic inhibition of vascular inflammation (oral salsalate; 1500 mg/twice daily, 4 days) would improve endothelium- and NO-dependent vasodilation in women with a history of preeclampsia (PE) but not in women with a history of uncomplicated pregnancy (HC). Twelve HC (30 ± 1yrs, 10 ± 2 months postpartum) and 10 PE (30 ± 2yrs, 8 ± 2 months postpartum) participated in a double-blind placebo-controlled study. Following each treatment, 2 intradermal microdialysis fibers were placed in the skin of the ventral forearm for graded infusion of acetylcholine (Ach, 10 -10 mM) or Ach + 15 mM L-NAME (NO synthase antagonist). Red blood cell flux was measured over each site by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and normalized to maximum (%CVC ; 28 mM SNP + local heat 43 °C). ACh-induced (77 ± 3 vs. 92 ± 3%CVC ; p = 0.01) and NO-dependent (20 ± 6 vs. 33 ± 4%; p = 0.02) vasodilation were attenuated in PE compared to HC. Salsalate augmented ACh-induced (95 ± 2%CVC ; p = 0.002) and NO-dependent (39 ± 3%; p = 0.009) dilation in PE compared to placebo but had no effect in HC (all p > 0.05). Salsalate treatment augmented endothelium-dependent vasodilation via NO-mediated pathways in women who have had preeclampsia, suggesting that inflammatory signaling mediates persistent endothelial dysfunction following preeclampsia.

Administration, Oral

Adult

Anti-Inflammatory Agents, Non-Steroidal - administration & dosage

Anti-Inflammatory Agents, Non-Steroidal - pharmacology

Double-Blind Method

Endothelium, Vascular - drug effects

Female

Humans

Microcirculation - drug effects

Pre-Eclampsia - drug therapy

Pre-Eclampsia - physiopathology

Pregnancy

Salicylates - administration & dosage

Salicylates - pharmacology

Skin - blood supply

Details

Title: Subtitle: Acute systemic inhibition of inflammation augments endothelium-dependent dilation in women with a history of preeclamptic pregnancy
Creators: Anna E Stanhewicz - University of Iowa
Gabrielle A Dillon - Pennsylvania State University
Corinna Serviente - Pennsylvania State University
Lacy M Alexander - Pennsylvania State University
Resource Type: Journal article
Publication Details: Pregnancy hypertension, Vol.27, pp.81-86
DOI: 10.1016/j.preghy.2021.12.010
PMID: 34973597
PMCID: PMC8858855
NLM abbreviation: Pregnancy Hypertens
ISSN: 2210-7789
eISSN: 2210-7797
Grant note: UL1 TR002537 / NCATS NIH HHS R00 HL138133 / NHLBI NIH HHS F32 HL129677 / NHLBI NIH HHS R01 HL093238 / NHLBI NIH HHS K99 HL138133 / NHLBI NIH HHS T32 AG049676 / NIA NIH HHS
Language: English
Date published: 03/2022
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984259393802771

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