Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction
Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction
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DOI：
10.1080/10641963.2017.1339073
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发表时间：
2018-01-01
影响因子：
12.3
通讯作者：
Resende, Angela C.
中科院分区：
文献类型：
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作者：
Amaral, Taline A. S.;Ognibene, Dayane T.;Resende, Angela C.
探讨硝基-L-精氨酸甲酯（L-NAME）诱导的实验性子痫前期（PE）的全身和胎盘氧化状态以及血管功能。比较四组之间的胎儿参数和母体血压、蛋白尿、肠系膜动脉床 (MAB) 反应性以及全身和胎盘氧化应激：妊娠大鼠在妊娠第 13 至 20 天接受 L-NAME（60 mg/kg/天，口服）（P + L-NAME）或载体 (P)，非妊娠大鼠在妊娠 7 天期间接受 L-NAME (NP + L-NAME) 或载体 (NP)。怀孕期间服用 L-NAME 会引发 PE 的一些症状，例如高血压和蛋白尿。与 P 组相比，P + L-NAME 组的体重增加和胎盘质量较低，活胎数量和体重也减少。 NP + L-NAME 和 P + L-NAME 灌注的 MAB 中由乙酰胆碱 (ACh) 和血管紧张素 II (Ang II) 诱导的血管舒张作用低于对照组。另外，NP + L-NAME 和 P + L-NAME 组的 MAB 中硝化甘油诱导的血管舒张以及去氧肾上腺素和 Ang II 诱导的血管收缩高于相应对照组。与对照组相比，P + L-NAME 组和 NP + L-NAME 组的全身和胎盘氧化损伤（通过丙二醛和羰基水平评估）增加，抗氧化酶超氧化物歧化酶和谷胱甘肽过氧化物酶的活性降低。目前的数据表明，氧化应激和一氧化氮生物利用度降低可能导致先兆子痫大鼠肠系膜对ACh和Ang II的血管舒张反应减弱，以及对Ang II的高反应性，这可能导致外周血管阻力和血压增加，以及L-NAME诱导的PE中宫内生长受限。
To investigate the systemic and placental oxidant status as well as vascular function in experimental preeclampsia (PE) induced by nitro-L-arginine methyl ester (L-NAME). Fetal parameters and maternal blood pressure, proteinuria, mesenteric arterial bed (MAB) reactivity, and systemic and placental oxidative stress were compared between four groups: pregnant rats receiving L-NAME (60 mg/kg/day, orally) (P + L-NAME) or vehicle (P) from days 13 to 20 of pregnancy and nonpregnant rats receiving L-NAME (NP + L-NAME) or vehicle (NP) during 7 days. L-NAME administration during pregnancy induced some hallmarks of PE, such as hypertension and proteinuria. The P + L-NAME group presented lower weight gain and placental mass as well as reduced number and weight of live fetuses than P group. The vasodilator effect induced by acetylcholine (ACh) and angiotensin II (Ang II) was lower in the perfused MAB from NP + L-NAME and P + L-NAME than in control groups. Otherwise, the nitroglycerine-induced vasodilation and the phenylephrine-and Ang II-induced vasoconstriction were higher in MAB from NP + L-NAME and P + L-NAME groups than in the respective controls. Systemic and placental oxidative damage, assessed by malondialdehyde and carbonyl levels, was increased and activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced in P + L-NAME and NP + L-NAME groups compared to controls. The present data suggest that the oxidative stress and reduced bioavailability of nitric oxide may contribute to attenuation of vasodilator responses to ACh and Ang II, and hyperreactivity to Ang II in the mesentery of preeclamptic rat, which may contribute to the increased peripheral vascular resistance and BP, as well as intrauterine growth restriction in L-NAME-induced PE.