Evidence for microvascular dysfunction after prenatal dexamethasone at 0.7, 0.75, and 0.8 gestation in sheep.

Evidence for microvascular dysfunction after prenatal dexamethasone at 0.7, 0.75, and 0.8 gestation in sheep.
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绵羊妊娠 0.7、0.75 和 0.8 周产前使用地塞米松后微血管功能障碍的证据。

DOI:
10.1152/ajpregu.00031.2002
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发表时间:
2002
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Nathanielsz,PeterW
Nathanielsz,PeterW
中科院分区:
--
文献类型:
--
作者:
Molnar,Judit;Nijland,MarkJM;Howe,DavidC;Nathanielsz,PeterW

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地塞米松(DM)给予妊娠母羊,每3周注射4次,每次2毫克,间隔12小时。从妊娠103天(dGA;足月~ 149天)开始给予DM (n= 7)或生理盐水(n= 7)。胎儿股动脉(内径~ 300 μm)在119ga时用钢丝肌造影评估。dm暴露的胎儿明显小于盐暴露的胎儿。DM暴露使最大收缩增加至125 mM KCl,最大张力随着内皮素-1的敏感性和缓激素的松弛而发展。用一氧化氮合酶抑制剂ng -硝基精氨酸甲酯预孵育使对照组内皮素-1和乙酰胆碱的剂量-反应曲线向右移动,而在dm暴露组则没有。两组对乙酰胆碱和一氧化氮供体硝普钠的松弛作用相似。内皮素诱导的血管收缩增强、内皮依赖性松弛异常和内皮非依赖性松弛正常的结合表明产前给药后微血管功能障碍。由于这种功能障碍与几种形式的成人高血压有关,我们的研究结果表明,产前糖皮质激素暴露对成人心血管健康的潜在影响。
Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of four injections of 2 mg at 12-h intervals. DM (n= 7) or saline (n= 7) was given starting at 103 days of gestation (dGA; term ∼149 days). Fetal femoral arteries (∼300-μm internal diameter) were evaluated using wire myography at 119 dGA. DM-exposed fetuses were significantly smaller than saline-exposed fetuses. DM exposure increased maximal contraction to 125 mM KCl, and maximum tension developed along with sensitivity to endothelin-1 and relaxation to bradykinin. Preincubation with the nitric oxide synthase inhibitorNG-nitro-l-arginine methyl ester shifted the dose-response curves to endothelin-1 and acetylcholine to the right in controls but not in the DM-exposed group. Relaxation to acetylcholine and to the nitric oxide donor sodium nitroprusside was similar in both groups. The combination of enhanced endothelin-induced vasoconstriction, abnormal endothelium-dependent relaxation, and normal endothelium-independent relaxation indicates microvessel dysfunction following antenatal DM administration. Because such dysfunction is associated with several forms of adult hypertension, our results indicate the potential for consequences of antenatal glucocorticoid exposure on adult cardiovascular health.
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