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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
Journal article   Open access   Peer reviewed

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), Vol.140(4), pp.983-992
04/2026
DOI: 10.1152/japplphysiol.01080.2025
PMCID: PMC13007222
PMID: 41758055
url
https://doi.org/10.1152/japplphysiol.01080.2025View
Published (Version of record) Open Access

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 with 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 whether 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 (10−10–10−1 M) and insulin (10−8–10−4 M) in women with a history of GDM and HC women in control sites (Lactated Ringer’s), sites treated with 15 mM l-NAME (NG-nitro-l-arginine methyl ester; nitric oxide synthase inhibitor), 100 µM apocynin (NADPH oxidase inhibitor), and 15 mM l-NAME combined with 100 µM apocynin. Women with a history of GDM had reduced acetylcholine- (P = 0.002) and insulin- (P = 0.006) mediated dilation responses compared with 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

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