Howarth S R, Vallance P, Wilson C A
Department of Obstetrics and Gynaecology, St George's Hospital Medical School, London, UK.
Placenta. 1995 Dec;16(8):679-89. doi: 10.1016/0143-4004(95)90012-8.
The possibility that the vasoconstrictor agents present in the circulation may mediate their effect on placental blood flow by stimulating local prostanoid production was investigated. Placental cotyledons obtained at term from normal pregnancies were perfused in vitro. The dose-related vasoconstrictor effects of endothelin-1 (ET-1), angiotensin II (A II) and 5-hydroxytryptamine (5 HT) were reduced by graded concentrations of the thromboxane A2 (TXA2) receptor antagonist GR32191 (10(-7)-10(-4)M), aspirin (10(-5)-10(-4)M) and indomethacin (10(-5)M). The effect of the TXA2 receptor agonist U46619 was totally abolished by GR32191 (10(-7)M) but unaffected by the prostanoid synthesis inhibitors, aspirin and indomethacin although they prevented a self-priming effect of U46619. When effluents were collected from perfused placentae, 5-10 min after administration of sub-maximal doses of ET-1 (20 pmol), A II (500 pmol) and 5 HT (15 pmol), there was a significant increase in TXB2, the stable metabolite of TXA2, indicating the vasoconstrictors had induced an increase in local prostanoid production. These findings indicate that the vasoconstrictor effects of ET-1, A II and 5 HT in the placental vascular bed are mediated, at least in part, by vasoconstrictor prostanoids including TXA2.
研究了循环系统中存在的血管收缩剂是否可能通过刺激局部前列腺素生成来介导其对胎盘血流的影响。从正常妊娠足月时获取的胎盘小叶进行体外灌注。血栓素A2（TXA2）受体拮抗剂GR32191（10⁻⁷ - 10⁻⁴M）、阿司匹林（10⁻⁵ - 10⁻⁴M）和吲哚美辛（10⁻⁵M）的不同浓度可降低内皮素-1（ET-1）、血管紧张素II（A II）和5-羟色胺（5 HT）的剂量相关血管收缩作用。TXA2受体激动剂U46619的作用可被GR32191（10⁻⁷M）完全消除，但不受前列腺素合成抑制剂阿司匹林和吲哚美辛的影响，尽管它们可阻止U46619的自增强作用。当从灌注的胎盘中收集流出液时，在给予次最大剂量的ET-1（20 pmol）、A II（500 pmol）和5 HT（15 pmol）后5 - 10分钟，TXA2的稳定代谢产物TXB2显著增加，表明血管收缩剂诱导了局部前列腺素生成增加。这些发现表明，ET-1、A II和5 HT在胎盘血管床中的血管收缩作用至少部分是由包括TXA2在内的血管收缩性前列腺素介导的。
