Prenatal lipopolysaccharide exposure causes mesenteric vascular dysfunction through the nitric oxide and cyclic guanosine monophosphate pathway in offspring
Prenatal lipopolysaccharide exposure causes mesenteric vascular dysfunction through the nitric oxide and cyclic guanosine monophosphate pathway in offspring
复制标题
产前脂多糖暴露通过一氧化氮和环磷酸鸟苷途径导致子代肠系膜血管功能障碍
DOI：
10.1016/j.freeradbiomed.2015.05.040
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Zeng Chunyu
中科院分区：
文献类型：
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作者：
Wang Xinquan;Wang Jialiang;Luo Hao;Chen Caiyu;Pei Fang;Cai Yue;Yang Xiaoli;Wang Na;Fu Jinjuan;Xu Zaichen;Zhou Lin;Zeng Chunyu
心血管疾病，如高血压，可能在胎儿期就被编程。产前子宫内脂多糖（LPS）分泌可导致后代血压升高，但其血管机制尚不清楚。在妊娠第8、10和12天，向妊娠Sprague-Dawley大鼠腹腔内注射LPS（0.79 mg/kg）或盐水（0.5 ml）。LPS处理的母鼠的后代有较高的血压和减少乙酰胆碱（ACh）诱导的舒张和增加苯肾上腺素（PE）诱导的收缩内皮完整的肠系膜动脉。内皮细胞的去除显着增强了PE诱导的收缩在后代的控制，但不是LPS处理的母鼠。预处理的动脉与l-NAME抑制内皮细胞中的一氧化氮合酶（eNOS）或ODQ抑制血管平滑肌中cGMP的产生衰减乙酰胆碱诱导的舒张，但增强PE诱导的收缩在更大程度上在动脉的控制比那些从LPS处理的母鼠的后代。此外，由硝普钠引起的非内皮依赖性舒张作用也在LPS处理的母鼠后代的动脉中降低。功能性结果伴随着eNOS和可溶性鸟苷酸环化酶（sGC）的表达减少，以及LPS处理的母鼠后代动脉中NO和cGMP的产生。此外，LPS处理的母鼠的后代动脉氧化应激增加，抗氧化能力下降。用TEMPOL（一种活性氧（ROS）清除剂）治疗三周，使ROS、eNOS和sGC水平的变化以及LPS治疗母鼠后代动脉中NO和cGMP的产生和血管功能正常化。总之，产前LPS暴露程序通过增加氧化应激和受损的NO-cGMP信号通路的肠系膜动脉血管功能障碍。
Cardiovascular diseases, such as hypertension, could be programmed in fetal life. Prenatal lipopolysaccharide (LPS) exposurein uteroresults in increased blood pressure in offspring, but the vascular mechanisms involved are unclear. Pregnant Sprague–Dawley rats were intraperitoneally injected with LPS (0.79 mg/kg) or saline (0.5 ml) on gestation days 8, 10, and 12. The offspring of LPS-treated dams had higher blood pressure and decreased acetylcholine (ACh)-induced relaxation and increased phenylephrine (PE)-induced contraction in endothelium-intact mesenteric arteries. Endothelium removal significantly enhanced the PE-induced contraction in offspring of control but not LPS-treated dams. The arteries pretreated withl-NAME to inhibit nitric oxide synthase (eNOS) in the endothelium or ODQ to inhibit cGMP production in the vascular smooth muscle had attenuated ACh-induced relaxation but augmented PE-induced contraction to a larger extent in arteries from offspring of control than those from LPS-treated dams. In addition, the endothelium-independent relaxation caused by sodium nitroprusside was also decreased in arteries from offspring of LPS-treated dams. The functional results were accompanied by a reduction in the expressions of eNOS and soluble guanylate cyclase (sGC) and production of NO and cGMP in arteries from offspring of LPS-treated dams. Furthermore, LPS-treated dam’s offspring arteries had increased oxidative stress and decreased antioxidant capacity. Three-week treatment with TEMPOL, a reactive oxygen species (ROS) scavenger, normalized the alterations in the levels of ROS, eNOS, and sGC, as well as in the production of NO and cGMP and vascular function in the arteries of the offspring of LPS-treated dams. In conclusion, prenatal LPS exposure programs vascular dysfunction of mesenteric arteries through increased oxidative stress and impaired NO–cGMP signaling pathway.