4.5 Article

Oxidative stress contributes to reductions in microvascular endothelial- and nitric oxide-dependent dilation in women with a history of gestational diabetes

期刊

JOURNAL OF APPLIED PHYSIOLOGY
卷 133, 期 2, 页码 361-370

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00189.2022

关键词

endothelial dysfunction; gestational diabetes; microvasculature; nitric oxide

资金

  1. University of Iowa Fraternal Order of Eagles Diabetes Research Center
  2. National Center for Advancing Translational Sciences [UL1TR002537]

向作者/读者索取更多资源

The study demonstrates that women who have had gestational diabetes during pregnancy are at higher risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. Microvascular dysfunction, mediated by increased oxidative stress, persists after pregnancy in women who had gestational diabetes.
Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease (CVD) and similar to 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 degrees C; 0.1 degrees 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 N-G-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 thorn 43 degrees 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 (R-2 = 0.53, P = 0.02) and NO-dependent (R-2 = 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. NEW & NOTEWORTHY Women who have gestational diabetes during pregnancy are at greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. However, the mechanisms mediating this increased risk are unclear. Herein, we demonstrate that microvascular dysfunction, mediated by increase in oxidative stress, persists after pregnancy in women who had gestational diabetes, despite the remission of glucose tolerance.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据