Martínez-Orgado José, González Rita, Alonso María J, Salaices Mercedes
Area de Pediatría y Neonatología, Fundación Hospital Alcorcón, Madrid, Spain.
J Soc Gynecol Investig. 2004 Feb;11(2):82-8. doi: 10.1016/j.jsgi.2003.08.003.
We studied fetal endothelial function in a model of preeclampsia induced by Nomega-nitro-l-arginine methylester (L-NAME) administration in pregnant rats.
Aortic segments from term fetuses and 2-day-old Wistar rats treated with L-NAME (0.5 mg/mL in drinking water) (fetuses from hypertensive rats, FH, and newborns from hypertensive rats, NH) and from untreated rats (fetuses from normotensive rats, FN, and newborns from normotensive rats, NN) were obtained. Endothelium-dependent and -independent relaxations were determined by the response to 1 microM acetylcholine (ACh) and 1 microM sodium nitroprusside (SNP), respectively, after precontraction with 3 microM prostaglandin F2alpha. The role of nitric oxide in ACh relaxation was assessed by incubation with 0.1 mM N(G)-monomethyl-l-arginine (L-NMMA) or 0.1 mM l-arginine (l-Arg). Precontraction with 50 mM potassium chloride assessed the role of hyperpolarizing mechanisms.
In FH, ACh-induced relaxation was reduced (FH 34.2 +/- 4%, FN 45.8 +/- 2%, P < .05), whereas that of SNP was enhanced (FH 68.4 +/- 5%, FN 50.4 +/- 4%, P < .05). l-Arg did not reverse the impairment of ACh relaxation. L-NMMA reduced ACh relaxation in FN but increased it in FH; this increase was abolished by potassium chloride precontraction and by 1 microM capsaicine, a calcitonin-gene related peptide inhibitor. The hyperpolarizing component of ACh relaxation was reduced in FH as compared with FN. By contrast, ACh relaxation was greater in NH than in NN, with the relative participation of nitric oxide and hyperpolarizing-related components being similar in both groups.
Fetal ACh relaxation was impaired in this preeclampsia-like model. This impairment is probably not exclusively an effect of L-NAME but could reflect endothelial dysfunction that disappears after birth.
我们在孕鼠中通过给予N-甲基-L-精氨酸甲酯（L-NAME）诱导的子痫前期模型中研究了胎儿内皮功能。
获取足月胎儿和用L-NAME（饮用水中0.5mg/mL）处理的2日龄Wistar大鼠（高血压大鼠的胎儿，FH，以及高血压大鼠的新生鼠，NH）和未处理大鼠（正常血压大鼠的胎儿，FN，以及正常血压大鼠的新生鼠，NN）的主动脉段。在用3μM前列腺素F2α预收缩后，分别通过对1μM乙酰胆碱（ACh）和1μM硝普钠（SNP）的反应来测定内皮依赖性和非依赖性舒张。通过与0.1mM N(G)-单甲基-L-精氨酸（L-NMMA）或0.1mM L-精氨酸（L-Arg）孵育来评估一氧化氮在ACh舒张中的作用。用50mM氯化钾预收缩评估超极化机制的作用。
在FH中，ACh诱导的舒张降低（FH 34.2±4%，FN 45.8±2%，P<.05），而SNP诱导的舒张增强（FH 68.4±5%，FN 50.4±4%，P<.05）。L-Arg不能逆转ACh舒张的损害。L-NMMA降低了FN中的ACh舒张，但增加了FH中的ACh舒张；这种增加被氯化钾预收缩和1μM辣椒素（一种降钙素基因相关肽抑制剂）消除。与FN相比，FH中ACh舒张的超极化成分降低。相比之下，NH中的ACh舒张大于NN中的，两组中一氧化氮和超极化相关成分的相对参与情况相似。
在这个子痫前期样模型中胎儿ACh舒张受损。这种损害可能不仅仅是L-NAME的作用，而是可能反映了出生后消失的内皮功能障碍。
