Sand A E, Andersson E, Fried G
Department of Women and Child Health, Division of Obstetrics and Gynecology, Karolinska Institute and Hospital, Sweden.
Acta Physiol Scand. 2002 Mar;174(3):217-23. doi: 10.1046/j.1365-201x.2002.00939.x.
In order to explore the role of nitric oxide (NO) in the control of fetoplacental vascular tone in normal pregnancy we have examined the effects of NO donors on uteroplacental arteries pre-contracted with the vasoconstrictor endothelin-1 (ET-1) or serotonin (5-HT). We have furthermore examined the effects of guanylate cyclase inhibitors on the NO-induced relaxation. Segments of placental arteries (n=102) obtained from 39 placentas immediately after delivery were mounted in organ baths and superfused with Krebs-Ringer solution at 37 degrees C. The vessel segments were exposed to drugs for various intervals and the tension was recorded isometrically and registered on a polygraph. Cyclic guanosine monophosphate (cGMP) analysis was performed after extraction of vessel segments using a specific radioimmunoassay. The placental artery segments responded to ET-1 and 5-HT with a dose-dependent vasoconstriction. After pre-contraction with ET-1 (10(-7) M) or 5-HT (10(-6) M), the vessels relaxed in response to the NO donors glyceryltrinitrate (GTN) (10(-6) M) and S-nitroso-N-acetyl-penicillamine (SNAP) (10(-5) M). In the presence of the non-specific guanylate cyclase inhibitor LY 83583 (10(-6) M), the vessels responded with a small contraction. In the presence of the soluble guanylate cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) the non-treated vessels responded with a relaxation. 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one gave no obvious relaxation in pre-contracted vessels. Addition of 8-Br-cGMP, the cell-permeant analogue of cGMP, with or without pre-contraction had no effect on the vessels. Cyclic guanosine monophosphate analysis showed that GTN treatment caused an increase in cGMP after 12 min. Our results indicate that NO acts as a vasodilator in placental vessels. The cGMP-dependent mechanisms may be involved in NO-induced relaxation but cGMP-independent mechanisms appear also to be involved.
为了探究一氧化氮（NO）在正常妊娠中对胎儿 - 胎盘血管张力控制的作用，我们研究了NO供体对预先用血管收缩剂内皮素 - 1（ET - 1）或5 - 羟色胺（5 - HT）预收缩的子宫胎盘动脉的影响。我们还研究了鸟苷酸环化酶抑制剂对NO诱导的舒张作用的影响。在分娩后立即从39个胎盘中获取胎盘动脉段（n = 102），将其安装在器官浴槽中，并在37℃下用Krebs - Ringer溶液进行灌流。将血管段暴露于各种药物不同时间，等长记录张力，并在记录仪上记录。使用特定的放射免疫分析法在提取血管段后进行环磷酸鸟苷（cGMP）分析。胎盘动脉段对ET - 1和5 - HT呈剂量依赖性血管收缩反应。在用ET - 1（10⁻⁷ M）或5 - HT（10⁻⁶ M）预收缩后，血管对NO供体硝酸甘油（GTN）（10⁻⁶ M）和S - 亚硝基 - N - 乙酰青霉胺（SNAP）（10⁻⁵ M）产生舒张反应。在存在非特异性鸟苷酸环化酶抑制剂LY 83583（10⁻⁶ M）的情况下，血管出现轻微收缩。在存在可溶性鸟苷酸环化酶（sGC）抑制剂1H[1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮（ODQ）时，未处理的血管出现舒张反应。1H[1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮在预收缩的血管中未产生明显舒张作用。添加8 - 溴 - cGMP（cGMP的细胞渗透性类似物），无论有无预收缩，对血管均无影响。环磷酸鸟苷分析表明，GTN处理12分钟后cGMP增加。我们的结果表明，NO在胎盘血管中起血管舒张剂的作用。cGMP依赖性机制可能参与NO诱导的舒张，但cGMP非依赖性机制似乎也参与其中。
