Journal article
Oxidative stress contributes to reductions in microvascular endothelial- and nitric oxide-dependent dilation in women with a history of gestational diabetes
Journal of applied physiology, Vol.133(2), pp.361-370
07/07/2022
DOI: 10.1152/japplphysiol.00189.2022
PMCID: PMC9359638
PMID: 35796611
Abstract
Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease (CVD) and ~7 times as likely to develop type 2 diabetes as their age-matched counterparts. However, the mechanism(s) mediating these associations remain unclear. We hypothesized that endothelium- and (nitric oxide) NO-dependent dilation would be attenuated through oxidant stress mechanisms in the microvasculature of women with a history of GDM compared with control women with a history of uncomplicated pregnancy (HC). Ten HC (35 ± 4 yr) and 10 GDM (34 ± 4 yr) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer's (control) or 5 mM L-ascorbate. After full expression of the local heating response, 15 mM NG-nitro-L-arginine methyl ester (NO synthase inhibition) was perfused. Red cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC = flux/MAP) was standardized to maximum (% CVCmax; 28 mM SNP + 43°C). Urine albumin:creatinine ratio (ACR) was measured. GDM had attenuated endothelium-dependent (GDM: 67 ± 7 vs. HC: 90 ± 4% CVCmax; P < 0.001) and NO-dependent (GDM: 54 ± 7 vs. HC: 71 ± 3% CVCmax; P = 0.001) dilation at the control site and tended to have higher urine ACR (P = 0.06). Both endothelium-dependent (R2 = 0.53, P = 0.02) and NO-dependent (R2 = 0.56, P = 0.01) dilation were related to urine ACR in GDM. L-ascorbate perfusion improved endothelium-dependent (82 ± 5% CVCmax; P = 0.03 vs. control) and NO-dependent (68 ± 5% CVCmax; P = 0.02 vs. control) dilation in GDM but had no effect in HC (P > 0.05). Otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and this dysfunction is mediated, in part, by oxidative stress.
Details
- Title: Subtitle
- Oxidative stress contributes to reductions in microvascular endothelial- and nitric oxide-dependent dilation in women with a history of gestational diabetes
- Creators
- Anna E Stanhewicz - University of IowaRowan L Schlarmann - University of IowaKaila M Brustkern - University of IowaDiana Jalal - Iowa City VA Health Care System
- Resource Type
- Journal article
- Publication Details
- Journal of applied physiology, Vol.133(2), pp.361-370
- DOI
- 10.1152/japplphysiol.00189.2022
- PMID
- 35796611
- PMCID
- PMC9359638
- ISSN
- 8750-7587
- eISSN
- 1522-1601
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa Fraternal Order of Eagles Diabetes Research Center; DOI: 10.13039/100006108, name: HHS | NIH | National Center for Advancing Translational Sciences, award: UL1TR002537
- Language
- English
- Date published
- 07/07/2022
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Nephrology; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984273657402771
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