Impact of maternal dexamethasone on coronary PGE(2) production and prostaglandin-dependent coronary reactivity.
Impact of maternal dexamethasone on coronary PGE(2) production and prostaglandin-dependent coronary reactivity.
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母体地塞米松对冠状动脉 PGE(2) 产生和前列腺素依赖性冠状动脉反应性的影响。
DOI：
10.1152/ajpregu.00658.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Segar,JeffreyL
中科院分区：
文献类型：
--
作者：
Roghair,RobertD;Volk,KennethA;Lamb,FredS;Segar,JeffreyL
宫内生长受限与胎儿糖皮质激素暴露增加和成人冠状动脉疾病风险增加有关。暴露于妊娠早期地塞米松（Dex）的绵羊冠状动脉对血管紧张素II （ANG II）的收缩增加。前列腺素E2（PGE2）有助于维持冠状动脉扩张，但给药后PGE2的产生急剧下降。我们假设妊娠早期接触Dex会损害成年冠状动脉pge2的产生，随后冠状动脉反应性增加。母羊妊娠27 ~ 28天（145天）给予Dex。在4月龄时（N= 5 ~ 7）用钢丝肌图评估后代的冠状动脉反应性。培养冠状动脉平滑肌细胞，用放射性标记的花生四烯酸酯孵育90分钟后测定前列腺素的产生。暴露于dex的羔羊的冠状动脉肌细胞的pge2产量显著下降，与ANG II孵育相反。dexx暴露的冠状动脉对angii的收缩增加，对花生四烯酸的扩张减弱，以摩擦灭活内皮后差异最大。环加氧酶（COX）抑制剂吲哚美辛的预孵育改变了对照反应，重现了右美托咪定暴露后冠状动脉压度升高。我们得出结论，冠状动脉平滑肌cox介导的pge2生成受损与妊娠早期Dex引起的冠状动脉功能障碍有关。程序性抑制血管舒张性前列腺素的产生可能与不良的宫内环境与成人冠状动脉疾病有关。
Intrauterine growth restriction is associated with increased fetal glucocorticoid exposure and an increased risk of adult coronary artery disease. Coronary arteries from sheep exposed to early gestation dexamethasone (Dex) have increased constriction to angiotensin II (ANG II). Prostaglandin E2(PGE2) helps maintain coronary dilation, but PGE2production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE2production with subsequent increases in coronary reactivity. Dex was administered to ewes at 27–28 days gestation (term 145 days). Coronary reactivity was assessed by wire myography in offspring at 4 mo of age (N= 5 to 7). Coronary smooth muscle cells were cultured and prostaglandin production was measured after 90 min incubation with radiolabeled arachidonate. Coronary myocytes from Dex-exposed lambs had a significant decrease in PGE2production that was reversed with ANG II incubation. Dex-exposed coronary arteries had increased constriction to ANG II and attenuated dilatation to arachidonic acid, with the greatest difference seen after the endothelium was inactivated by rubbing. Preincubation with the cyclooxygenase (COX) inhibitor indomethacin altered control responses and recapitulated the heightened coronary tone seen following Dex exposure. We conclude that impaired coronary smooth muscle COX-mediated PGE2production contributes to the coronary dysfunction elicited by early gestation Dex. Programmed inhibition of vasodilatory prostanoid production may link an adverse intrauterine environment with adult coronary artery disease.
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DOI：
10.1152/ajpregu.00369.2005
发表时间：
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期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
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作者：
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期刊：
American journal of physiology. Heart and circulatory physiology
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