Izumi H, Makino Y, Mohtai H, Shirakawa K, Garfield R E
Department of Obstetrics and Gynecology, Fukuoka University School of Medicine, Japan.
Am J Obstet Gynecol. 1996 Aug;175(2):375-81. doi: 10.1016/s0002-9378(96)70149-7.
We intended to compare the relative importance of nitric oxide and prostacyclin as endothelium-derived vasorelaxing factors released by histamine in human umbilical artery at the midstage (18 to 22 weeks) of gestation.
By use of very thin muscle strips, which allows rapid diffusional access of applied drugs (in a few seconds), isometric tensions were recorded in response to histamine. The histamine-induced contractions and the relaxing effect of histamine on the potassium chloride (39 mmol/L) contractions were studied in relation to the existence of endothelium, L-NG-nitro arginine, and indomethacin. The relaxing effects of glyceryl trinitrate and prostacyclin on the potassium chloride contractions were also examined.
The contractile responses to histamine were more sensitive and the relation tensions of histamine contractions, compared with the 39 mmol/L K(+)-induced contractions, were large in endothelium-denuded strips than in endothelium-intact strips. Histamine contractions were enhanced in endothelium-intact strips in the presence of 10 mumol/L L-NG-nitro arginine (competitive inhibitor of nitric oxide synthase) but not in the presence of 10 mumol/L indomethacin (cyclooxygenase inhibitor). Histamine produced a concentration-dependent relaxation during the maintained contraction induced by 39 mmol/L K+. These histamine-induced relaxations were completely blocked by L-NG-nitro arginine but not by indomethacin. Glyceryl trinitrate and prostacyclin relaxed the sustained contractions induced by 39 mmol/L K+ in a dose-dependent manner; however, the degree of relaxation by glyceryl trinitrate was more prominent than that by prostacyclin.
These results suggest that nitric oxide is more potent than prostacyclin as a vasorelaxing substance released from the endothelium and that nitric oxide has an important role for controlling fetoplacental circulation at midgestation.
我们旨在比较一氧化氮和前列环素作为组胺在妊娠中期(18至22周)人脐动脉中释放的内皮源性血管舒张因子的相对重要性。
使用非常细的肌条,这使得应用药物能够在几秒钟内快速扩散进入,记录对组胺的等长张力。研究了组胺诱导的收缩以及组胺对氯化钾(39 mmol/L)收缩的舒张作用与内皮、L-NG-硝基精氨酸和吲哚美辛存在的关系。还检查了硝酸甘油和前列环素对氯化钾收缩的舒张作用。
与39 mmol/L钾离子诱导的收缩相比,对组胺的收缩反应更敏感,且在内皮剥脱的肌条中组胺收缩的相对张力大于内皮完整的肌条。在存在10 μmol/L L-NG-硝基精氨酸(一氧化氮合酶的竞争性抑制剂)时,内皮完整的肌条中组胺收缩增强,但在存在10 μmol/L吲哚美辛(环氧化酶抑制剂)时则不然。在由39 mmol/L钾离子诱导的持续收缩期间,组胺产生浓度依赖性舒张。这些组胺诱导的舒张被L-NG-硝基精氨酸完全阻断,但不被吲哚美辛阻断。硝酸甘油和前列环素以剂量依赖性方式舒张由39 mmol/L钾离子诱导的持续收缩;然而,硝酸甘油的舒张程度比前列环素更显著。
这些结果表明,作为从内皮释放的血管舒张物质,一氧化氮比前列环素更有效,并且一氧化氮在控制妊娠中期胎儿胎盘循环中具有重要作用。