Control of vascular tone by endothelium-derived relaxing and hyperpolarizing factors

内皮源性舒张因子和超极化因子对血管张力的控制

• 批准号: 07670786
• 负责人: NAKAYA Yutaka
• 金额: $ 1.47万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670786/
• 关键词: artery; endothelium; vascular smooth muscle cells; nitric oxide; endothelium-derived relaxing factor; patch clamp

Control of vascular tone by endothelium-derived relaxing (EDRF) and hyperpolarizing factors (EDHF) was studied in cultured porcine coronary artery smooth muscle cells and endothelial cells using patch clamp techniques. We characterized two major K channels in smooth muscle cells, i.e.ATP sensitive K channel (KATP) and Ca^<2+>-activated K channels (Kca) and studied the target channels for EDRF and EDHF.These channels were targets organs of various vasoactive substances as well, and many vasoactive aubstances exert their actions through thses channels.In cell-attached patches, EDRF,which is known as nitric oxide (NO), activated Kca channel of smooth muscle cells via production of cGMP.We also found that NO also activated KATP channels and hyperpolarized membrane. In inside-out patches NO did not activated thses channels. We also studied the effect of EDHF on the ionic channles of smooth muslce cells, where is located close to the coronary artery strips with intact endothelium. In the pre … More sence of N^G-monomethyl L-arginine (LNMMA) and indomethacine, acetylcholine activated Kca channels of smooth muscle, suggesting that the target of EDHF was Kca channels. Tetraethylammonium and charybdotoxin, specific Kca channel blockers, suppressed this channels but glibenclamide, a specific KATP channel blocker, did not significantly altered the channel activity.We also found new pathway for production of NO from endothelium of porcine coronary artery and aorta. Different from previous studies, histamine did not increased cytosolic Ca^<2+> in endothelium but increased cAMP in endothelium. Histamine produced NO in the presence of histamine H_1 receptor antagonist, but NO production was significantly suppressed in the presence of H_2 receptor antagonist, suggesting that the histamine-induced NO production was mediated by H_2 receptor and through cAMP production. Amrinone, a phosphodiesterase inhibitor, and folskoline, an activator of adenylate cyclase, produced NO from porcine endothelium. These results indicated that there in a new pathway of NO production and that NO is produced by increasing cAMP without increase in cytosolic Ca^<2+>. Less

应用膜片钳技术研究了内皮源性舒张因子（EDRF）和超极化因子（EDHF）对猪冠状动脉平滑肌细胞和内皮细胞血管张力的调控作用。本文报道了平滑肌细胞中两种主要的钾通道，即ATP敏感性钾通道（KATP）和Ca ~（2+）激活性钾通道（Kca），并对EDRF和EDHF的靶通道进行了研究。这两种钾通道也是多种血管活性物质的靶器官，许多血管活性物质通过这两种钾通道发挥作用。在细胞贴附的膜片中，EDRF，即一氧化氮（NO），NO通过产生cGMP激活平滑肌细胞KCa通道，同时也激活KATP通道，使平滑肌细胞膜超极化。在由内而外的贴片中，NO不激活这些通道。我们还研究了EDHF对离体冠状动脉平滑肌细胞离子通道的影响。在预 ...更多信息 在吲哚美辛（indomethacine）和N^G-单甲基L-精氨酸（LNMMA）存在下，乙酰胆碱激活平滑肌Kca通道，提示EDHF作用的靶点是Kca通道。特异性Kca通道阻滞剂四乙铵和charybdotoxin抑制了该通道，但特异性KATP通道阻滞剂格列本脲并未显着改变通道活性。我们还发现了猪冠状动脉和主动脉内皮产生NO的新途径。与以往研究不同的是，组胺不增加内皮细胞胞浆Ca^<2+>，但增加内皮细胞cAMP。组胺H_1受体拮抗剂可诱导NO产生，而H_2受体拮抗剂可显著抑制NO的产生，提示组胺诱导NO的产生是由H_2受体介导的，并通过cAMP的产生。磷酸二酯酶抑制剂氨力农和腺苷酸环化酶激活剂Folskoline从猪内皮细胞产生NO。这些结果表明，NO的产生存在一条新的途径，NO是通过增加cAMP而产生的，而不增加胞浆Ca^<2+>。少

项目成果

Nameda Y ; Miyoshi H ; Tsuchiya K ; Nakaya Y ; Arase S: "Endotoxin-induced L-arginine pathway produces nitric oxide and modulates the Ca2+-activated K+ channel in cultured human dermal papilla cells." J Invest Dermatol. 106 (2). 342-5 (1996)

命名日 ;

Kazushi Minami: "Protein kinase C-independent inhibition of the Ca^<2+>-activated K^+ channel by angiotensin II and endthelin I" Biochemical Pharmacology. 49. 1051-1056 (1995)

Kazushi Minami：“血管紧张素II和内皮素I对Ca 2+ 激活的K 2 通道的蛋白激酶C独立抑制”生化药理学。

Fumiko Kishi: "Intracellular and extracellular Ca^<2+> regulate histamine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes" Pharmacological Research. 33. 123-126 (1996)

Fumiko Kishi：“细胞内和细胞外 Ca^2 调节血管内皮细胞中组胺诱导的一氧化氮释放，如敏感和选择性一氧化氮电极所示”药理学研究。

Nakaya Y: "Channels sensitive to glibenclamide in vascular smooth muscle cells. on "Recent Advances in Basic Mechanisms of Smooth Muscle Excitation"" Academic Press(in press),

Nakaya Y：“血管平滑肌细胞中对格列本脲敏感的通道。关于“平滑肌兴奋基本机制的最新进展””学术出版社（正在印刷中），

Hirokazu Miyoshi: "Calcitonin gene-related peptide activates the K^+ channels of vascular smooth muscle cells via adenvlate cyclase" Basic Res Cardiol. 90. 332-336 (1995)

Hirokazu Miyoshi：“降钙素基因相关肽通过腺苷酸环化酶激活血管平滑肌细胞的 Kk 通道”Basic Res Cardiol。