Research for the role of endothelium-dependent relaxation in the change of maternal circulation during pregnancy

内皮依赖性舒张在孕期母体循环变化中作用的研究

• 批准号: 13671700
• 负责人: SAKAMOTO Shuichi
• 金额: $ 0.7万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671700/
• 关键词: Hind-limb perfusion model; CCh-induced relaxation; EDHF; K^+ ion; metabolite(s) of P_<450> mono-oxygenase; ラット下肢潅流モデル; ラットの下肢潅流モデル; 内皮依存性脱分極因子(EDHF); K^+; 妊娠; 末梢血管抵抗; 下肢還流モデル; H_2O_2; 末梢血管; 一酸化窒素(NO); 内皮依存性過分極因子(EDHF)

We examined the involvement of NO and/or EDHF in decreasing peripheral vascular resistance in hind limb perfusion model of the rat, and analyzed the identity of EDHF in this model. The potency of carbachol (CCh) to produce relaxation was quantitatively similar to sodium nitroprusside (SNP). CCh-induced relaxation was abolished after endothelial denudation, but resistant to nitroarginine and indomethacin. The relaxation was inhibited by tetraethylammonium, ouabain, charybdotoxin plus apamin and under depolarization. SNP-induced relaxation was accompanied by the increased cGMP production, which was inhibited by ODQ. Although carbachol produced similar extent of relaxation to SNP, cGMP level was 24 times lower than that with SNP. Low KCI produced a definite relaxation, which was inhibited by ouabain, but independent of NO, prostacyclin and endothelium. 1-EBIO as an activator of IK_<Ca> channel also produced a concentration-dependent relaxation, which was inhibited by charybdotoxin, ouabai … More n and depolarization, but independent of NO and prostacyclin. Clotrimazole and 17-octadecynoic acid as inhibitors of P_<450> mono-oxygenase inhibited the carbachol-induced relaxation. Meanwhile, catalase at a concentration sufficient to inhibit H_2O_2- induced relaxation did not exert definite inhibition of the carbachol-induced relaxation. These results suggest that carbachol produces an endothelium-dependent, EDHF-dependent and NO-cGMP independent relaxation and that K^+ and metabolite(s) of P_<450> mono-oxygenase possibly play an important role for this relaxation. We also we investigated whether the responsiveness of peripheral resistant vessels of the hind limb changes during pregnancy, and the contribution of NO and EDHF to these changes was pharmacologically analyzed using a hind-limb perfusion model of the rat. In the end stage of pregnancy, peripheral vascular resistance was decreased in our model. The enhanced decrease in the peripheral vascular resistance, which is mediated by EDHF and partly due to the increased sensitivity of the pathway downstream the cGMP generation, possibly results in lowering the blood pressure and hyporesposiveness to vasoconstrictors at the term gestation of the rat. Less

我们在大鼠后肢灌注模型中检查了 NO 和/或 EDHF 在降低外周血管阻力中的作用，并分析了该模型中 EDHF 的特性。 卡巴胆碱 (CCh) 产生松弛的效力在数量上与硝普钠相似。 (SNP) 在内皮剥脱后消除了 CCh 诱导的松弛，但对硝基精氨酸和吲哚美辛具有抗性，该松弛被抑制。四乙铵、哇巴因、卡里布毒素加阿帕明和去极化下，伴随着cGMP产生的增加，这被ODQ抑制，尽管卡巴胆碱产生与SNP相似的松弛程度，但cGMP水平比SNP低24倍。低 KCI 产生明显的松弛，这种松弛受到哇巴因的抑制，但与 NO、前列环素和内皮细胞无关。 1-EBIO 作为 IK_<Ca> 通道的激活剂也产生浓度依赖性松弛，该松弛受到 Charybdotoxin、ouabai … 更多 n 和去极化的抑制，但不依赖于作为 P_ 抑制剂的 NO 和前列环素和 17-十八氰酸。 <450>单加氧酶抑制卡巴胆碱诱导的松弛，同时，过氧化氢酶的浓度足以抑制。 H_2O_2-诱导的舒张并未对卡巴胆碱诱导的舒张产生明确的抑制作用。这些结果表明，卡巴胆碱产生内皮依赖性、EDHF依赖性和NO-cGMP独立的舒张作用，并且K^+和P_<450的代谢物。 > 单加氧酶可能在这种松弛中发挥重要作用，我们还研究了妊娠期间后肢外周抵抗血管的反应性是否发生变化，以及 NO 和 EDHF 对这种松弛的贡献。使用大鼠后肢灌注模型对这些变化进行药理学分析。在我们的模型中，外周血管阻力下降，这是由 EDHF 介导的，部分原因是由于。 cGMP 生成下游途径的敏感性增加，可能导致妊娠足月大鼠的血压降低和对血管收缩剂的反应性降低。

项目成果

R.Loyaga, S.Sakamoto, T.Aso, Y.Yamauchi, H.Azuma: "Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat"Proceeding of 54th annual congress of the Japan society of obstetrics and gynecology. 39-44 (2002)

R.Loyaga、S.Sakamoto、T.Aso、Y.Yamauchi、H.Azuma：“大鼠妊娠期间外周阻力血管反应性的变化”日本妇产科学会第 54 届年会论文集。

Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat.

大鼠妊娠期间外周抵抗血管反应性的变化。

• 发表时间: 2002
• 期刊: Proceedings of 54^th Annual Congress of the Japan Society of Obstetrics and Gynecology
• 作者: R.Loyaga;S.Sakamoto;T.Aso;Y.Yamauchi;H.Azuma
• 通讯作者: H.Azuma

R.Loyaga, S.Sakamoto, et al.: "EDHF in the vasodilation of the peripheral resistant vessels of the rat"Journal of Pharmacological Sciences. 94 suppl 1. (2004)

R.Loyaga、S.Sakamoto 等人：“EDHF 对大鼠外周抵抗血管的血管舒张作用”《药理学科学杂志》。

Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat

大鼠妊娠期外周抵抗血管反应性的变化

• 发表时间: 2002
• 期刊: Proceedings of 54^<th> Annual Congress of the Japan Society of Obstetrics and Gynecology
• 作者: R.Loyaga;S.Sakamoto;T.Aso;Y.Yamauchi;H.Azuma
• 通讯作者: H.Azuma