Abstract
Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Women With a History of Gestational Diabetes
The FASEB journal, Vol.36, p.n/a
05/2022
DOI: 10.1096/fasebj.2022.36.S1.R2126
Abstract
Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease as their age‐matched counterparts. GDM is associated with endothelial dysfunction and elevated oxidative stress during pregnancy, and vascular dysfunction postpartum. However, the mechanism(s) mediating this postpartum dysfunction are unknown. Using the cutaneous circulation as a model, we examined if oxidative stress contributes to microvascular dysfunction in healthy women with a history of GDM (GDM). We hypothesized that: 1) endothelium‐ and nitric oxide (NO)‐dependent dilation would be attenuated in GDM compared to women with a history of normal pregnancy (NP), and 2) local antioxidant (L‐ascorbate) administration would augment endothelium‐ and NO‐dependent dilation in GDM. Ten NP (35±1yrs) and 10 GDM (34±1yrs) 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 5mM ascorbate. After full expression of the local heating response, 15mM NG‐nitro‐L‐arginine methyl ester (L‐NAME; 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; 28mM SNP + 43°C). Urine albumin to creatinine ratio (ACR) and plasma concentrations of oxidized LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) were measured. Women with history of GDM had attenuated endothelium‐dependent (GDM: 67±7 vs. NP: 90±4%CVCmax; p<0.001) and NO‐dependent (GDM: 54±7 vs. NP: 71±3%; 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. Local ascorbate perfusion improved endothelium‐dependent (82±5%CVCmax; p=0.03 vs. control) and NO‐dependent (68±5%; p=0.02 vs. control) dilation in those with history of GDM but had no effect in HC (p>0.05). There were no differences in plasma oxLDL (hxGDM:60.5 vs hxNP:50.9 U/L; p=0.18) or TBARS (hxGDM: 0.3 vs hxNP: 0.2 μM; p=0.26) concentrations between groups. These data suggest that otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and that this dysfunction is mediated, in part, by oxidative stress at the level of the vasculature.
Details
- Title: Subtitle
- Oxidative Stress Contributes to Microvascular Endothelial Dysfunction 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 I. Jalal - Iowa City VA Medical Center
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.36, p.n/a
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2022.36.S1.R2126
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- University of Iowa Fraternal Order of Eagles Diabetes Research Center
- Language
- English
- Date published
- 05/2022
- Academic Unit
- Nephrology; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984267155702771
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