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

本研究在大鼠后肢灌流模型中检测了NO和/或EDHF在降低外周血管阻力中的作用，并分析了EDHF在该模型中的身份。卡巴胆碱（CCh）产生松弛的效力在数量上与硝普钠（SNP）相似。内皮剥脱后，Cch诱导的舒张被取消，但对硝基精氨酸和吲哚美辛有抵抗力。四乙铵、哇巴因、蜂毒加蜂毒明和去极化均能抑制这种舒张作用。SNP诱导的舒张伴随着cGMP产生的增加，这是由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可产生一定的舒张作用，但不依赖于NO、前列环素和内皮细胞，可被哇巴因抑制。1-EBIO作为IK_2通道的激活剂<Ca>也产生浓度依赖性的舒张作用，这种作用可被蛇毒、哇巴因抑制 ...更多信息 n和去极化，但不依赖于NO和前列环素。克霉唑和17-十八炔酸作为P_单加氧酶的抑制剂<450>抑制卡巴胆碱引起的舒张。而足以抑制H_2O_2诱导的松弛的过氧化氢酶对卡巴胆碱诱导的松弛没有明显的抑制作用。这些结果提示卡巴胆碱具有内皮依赖性、EDHF依赖性和NO-cGMP非依赖性的舒张作用，K^+和P_单加氧酶代谢产物<450>可能在这种舒张作用中起重要作用。我们还调查了是否在怀孕期间后肢外周阻力血管的反应性的变化，和NO和EDHF对这些变化的贡献是使用大鼠后肢灌流模型的间接分析。在妊娠末期，外周血管阻力降低。EDHF介导的外周血管阻力的增强降低，部分是由于cGMP生成下游途径的敏感性增加，可能导致大鼠妊娠晚期血压降低和对血管收缩剂的反应性降低。少

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