Prenatal cocaine exposure causes sex-dependent impairment in the myogenic reactivity of coronary arteries in adult offspring.
Prenatal cocaine exposure causes sex-dependent impairment in the myogenic reactivity of coronary arteries in adult offspring.
复制标题
产前接触可卡因会导致成年后代冠状动脉肌源性反应性的性别依赖性损害。
DOI：
10.1161/hypertensionaha.109.138024
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Xiao D;Yang S;Zhang L
滥用可卡因是孕妇中的一个严重问题。本研究验证了产前可卡因暴露损害成年后代冠状动脉肌源性反应的假设。孕鼠从孕龄第15天到第21天接受可卡因（30 mg/kg-1天-1）或生理盐水，并在3个月大的后代中进行实验。在加压冠状动脉间隔动脉，直径和血管壁细胞内Ca 2+浓度同时测量在同一组织作为腔内压力的函数。在雄性或雌性中，CO2不影响KCl诱导的冠状动脉收缩，但降低了雄性血管的扩张性。在雄性后代中，可卡因治疗导致压力依赖性肌源性收缩显著下降。用NG-硝基-L-精氨酸抑制eNOS并不改变生理盐水对照或可卡因处理的动物中的肌源性反应。在女性中，可卡因导致压力依赖性肌源性收缩显著增加。NG-硝基-L-精氨酸不影响对照动物的肌源性反应，但阻断可卡因介导的作用。在男性和女性中，可卡因和生理盐水组之间的血管壁Ca 2+浓度的压力诱导的增加没有显着差异。可卡因处理后，在预冲洗动脉中的直径与Ca 2+浓度的变化的比率在雄性中显著较小，但在雌性后代中较大。结果表明，产前可卡因暴露导致冠状动脉肌源性张力通过改变Ca 2+敏感性的性别依赖性的方式重新编程，导致成年后代冠状动脉自动调节功能障碍的风险增加。
Cocaine abuse is a significant problem among pregnant women. The present study tested the hypothesis that prenatal cocaine exposure impairs myogenic reactivity of coronary arteries in adult offspring. Pregnant rats received cocaine (30 mg kg−1 day−1) or saline from days 15 to 21 of gestational age and experiments were conducted in 3-month-old offspring. In pressurized coronary septal arteries, the diameter and vessel wall intracellular Ca2+ concentrations were measured simultaneously in the same tissue as a function of intraluminal pressure. Cocaine did not affect KCl-induced contractions of coronary arteries in either males or females, but decreased the distensibility in male vessels. In male offspring, cocaine treatment resulted in a significant decease in pressure-dependent myogenic contractions. Inhibition of eNOS with NG-nitro-L-arginine did not alter the myogenic response in either saline control or cocaine-treated animals. In females, cocaine caused a significant increase in pressure-dependent myogenic contractions. NG-nitro-L-arginine did not affect the myogenic response in the control animals, but blocked the cocaine-mediated effect. In both males and females, the presure-induced increases in vessel wall Ca2+ concentrations were not significantly different between cocaine and saline groups. The ratio of changes in the diameter to Ca2+ concentrations in the presurized arteries was significantly less in male but greater in female offspring after cocaine treatment. The results suggest that prenatal cocaine exposure causes reprogramming of coronary myogenic tone via changes in the Ca2+ sensitivity in a sex-dependent manner, leading to an increased risk of dysfunction of coronary autoregulation in adult offspring.