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 - 10-1M) and insulin (10-8-10-4M) in women with a history of GDM and HC women in control sites (Lactated Ringer's), sites treated with 15mM L-NAME (NG-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.
Maurer et al. (Fri,) studied this question.