Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes

Grace S Maurer; Brian T O'Neill; Diana I Jalal; Anna E Stanhewicz

doi:10.1152/japplphysiol.01080.2025

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Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes

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Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes

Grace S Maurer, Brian T O'Neill, Diana I Jalal and Anna E Stanhewicz

Journal of applied physiology (1985)

02/27/2026

DOI: 10.1152/japplphysiol.01080.2025

PMCID: PMC13007222

PMID: 41758055

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https://pmc.ncbi.nlm.nih.gov/articles/PMC13007222/View

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Abstract

Women with a history of gestational diabetes mellitus (GDM) are at a significantly greater risk of developing cardiovascular disease and type 2 diabetes compared to healthy control (HC) women who had an uncomplicated pregnancy. Microvascular endothelial dysfunction, mediated in part by elevated oxidative stress, persists after pregnancy complicated by GDM. We examined if locally reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived oxidative stress using apocynin would improve acetylcholine- and insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of GDM. We evaluated in vivo microvascular endothelium-dependent vasodilator function by assessing cutaneous vascular conductance responses to graded infusions of acetylcholine (10 - 10 M) and insulin (10 -10 M) in women with a history of GDM and HC women in control sites (Lactated Ringer's), sites treated with 15mM L-NAME (N -nitro-l-arginine methyl ester; nitric oxide synthase inhibitor), 100µM apocynin (NADPH oxidase inhibitor), and 15mM L-NAME combined with 100µM apocynin. Women with a history of GDM had reduced acetylcholine- (p=0.002) and insulin- (p=0.006) mediated dilation responses compared to HC women. Local NADPH oxidase inhibition with apocynin improved acetylcholine-mediated (p=0.003) but not insulin-mediated (p=0.169) dilation in women with a history of GDM. Attenuations in microvascular vasodilation responses to acetylcholine are mediated, in part, by NADPH oxidase-derived oxidative stress. Our findings suggest that NADPH oxidase may be a viable therapeutic target to reduce future disease risk in women with a history of GDM.

endothelial function

microvascular

apocynin

gestational diabetes

Details

Title: Subtitle: Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes
Creators: Grace S Maurer - University of Iowa
Brian T O'Neill - University of Iowa
Diana I Jalal - University of Iowa
Anna E Stanhewicz - University of Iowa
Resource Type: Journal article
Publication Details: Journal of applied physiology (1985)
DOI: 10.1152/japplphysiol.01080.2025
PMID: 41758055
PMCID: PMC13007222
NLM abbreviation: J Appl Physiol (1985)
ISSN: 1522-1601
eISSN: 1522-1601
Grant note: HL169201 / HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) UL1TR002537 / HHS | NIH | National Center for Advancing Translational Sciences (NCATS)
Language: English
Electronic publication date: 02/27/2026
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Nephrology; Endocrinology and Metabolism; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9985139492402771

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