Elucidation of vasoreactive diversity induced by bradykinin -studies of G-proteins function and bradykinin metabolism -

缓激肽诱导的血管反应多样性的阐明 -G 蛋白功能和缓激肽代谢的研究 -

• 批准号: 13660302
• 负责人: MIYAMOTO Atsushi
• 金额: $ 2.18万
• 依托单位: Kagoshima 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-13660302/
• 关键词: Bradykinin; Basilar artery; Vasoreactivity; Tyrosine phosphorylation; cultured endothelial cell; NO production; Losartan; HOE140; G-蛋白質; チロシンキナーゼ阻害薬; チロシンフォスファターゼ阻害薬; 冠状動脈; ブタ; ウシ

(1)Nitric oxide (NO) is spontaneously released from cultured porcine basilar arterial endothelial cells under no stimulation conditions. Bradykinin (BK) enhanced the NO production in a concentration-dependent manner. The enhanced NO production was inhibited by treatments of a selective B_2 receptor antagonist, HOE140, or a NO synthase inhibitor, L-nitro-arginine.(2)Angiotensin (Ang) II induced a contraction in isolated porcine basilar arterial ring. A selective B_2 antagonist, HOE140, inhibited the AngII-induced contraction, while an Ang converting enzyme (ACE) inhibitor, captopril, enhanced the Ang II-induced contraction.(3)BK induces endothelium-dependent relaxation following by contraction in isolated porcine basilar arterial ring. In the presence of L-nitro-arginine (10^<-4> M), BK induced contraction but not relaxation. The BK-induced contraction was not inhibited by a selective AT_1 receptor antagonist, losartan.These results suggest that there might be some interaction between bradykinin and Ang receptors. Further experiments appears to be needed in this point.

（1）培养的猪基底动脉内皮细胞在无刺激条件下可自发释放一氧化氮（NO）。缓激肽（BK）以浓度依赖性方式促进NO的产生。选择性B_2受体拮抗剂HOE 140或NO合成酶抑制剂L-硝基精氨酸可抑制NO的产生。（2）血管紧张素（Ang）Ⅱ可引起离体猪基底动脉环收缩。选择性B_2受体拮抗剂HOE 140可抑制Ang Ⅱ引起的收缩，而血管紧张素转换酶（ACE）抑制剂卡托普利则增强Ang Ⅱ引起的收缩。(3)BK在离体猪基底动脉环中诱导内皮依赖性舒张，随后是收缩。在L-硝基精氨酸（10 μ M）存在下<-4>，BK引起收缩但不舒张。血管紧张素Ⅱ（Ang）受体拮抗剂氯沙坦（Losartan）不抑制BK引起的收缩，提示缓激肽与Ang受体之间可能存在相互作用。在这一点上似乎需要进一步的实验。

项目成果

Miyamoto, A., Murata, S., Nishio, A.: "Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery."Naunyn-Schmiedeberg's Archives of Pharmacology. 365. 365-370 (2002)

Miyamoto, A.、Murata, S.、Nishio, A.：“ACE 和 NEP 在缓激肽诱导的离体猪基底动脉松弛和收缩反应中的作用。”Naunyn-Schmiedeberg 的药理学档案。

Atsushi Miyamoto, Shin Murata, Akira Nishio: "Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery."Naunyn-Schmiedeberg's Arch.Pharmacol. 365. 365-370 (2002)

Atsushi Miyamoto、Shin Murata、Akira Nishio：“ACE 和 NEP 在缓激肽诱导的离体猪基底动脉松弛和收缩反应中的作用。”Naunyn-Schmiedeberg 的 Arch.Pharmacol。