通过钾离子通道、5,6-环氧二十碳三烯酸（5,6-EET）和缝隙连接介导内皮衍生超极化因子（EDHF）诱导的平滑肌细胞内钙离子浓度（[Ca(2+)](i)）降低和小动脉扩张。

Mediation of EDHF-induced reduction of smooth muscle [Ca(2+)](i) and arteriolar dilation by K(+) channels, 5,6-EET, and gap junctions.

作者信息

Ungvari Z, Koller A

机构信息

Department of Pathophysiology, Semmelweis University of Medicine, Budapest, Hungary.

出版信息

Microcirculation. 2001 Aug;8(4):265-74. doi: 10.1038/sj/mn/7800080.

DOI:10.1038/sj/mn/7800080

PMID:11528534

Abstract

OBJECTIVE

To characterize the role of K(+) channels, the cytochrome P-450 (CYP) metabolite 5,6-EET, and gap junctions in modulation of arteriolar myogenic tone by a non-nitric oxide nonprostaglandin mediator, termed "endothelium-dependent hyperpolarizing factor" (EDHF), released to acetylcholine (ACh) in skeletal muscle arterioles.

METHODS

In isolated rat gracilis arterioles, simultaneous changes in smooth muscle (aSM) Ca(2+) (assessed by changes in fura-2 ratiometric signal, R(Ca)) and diameter were measured in response to ACh in the presence of indomethacin and L-NAME.

RESULTS

ACh, the K(ATP) channel opener pinacidil, and the Ca(2+) channel inhibitor verapamil elicited comparable decreases in aSM Ca(2+) (max.: -32 +/- 3%, 29 +/- 3%, and -30 +/- 3%, respectively) and arteriolar dilations (max.: 90 +/- 4%, 96 +/- 2%, and 95 +/- 2%, respectively). ACh-induced responses were inhibited by KCl-depolarization, K(Ca) channel blockers (TEA, charybdotoxin), or gap junction inhibitors (18alpha-glycyrrhetinic acid, hyperosmolar sucrose). The K(ATP) channel inhibitor glibenclamide, the K(IR) channel inhibitor barium chloride, or the CYP inhibitor 17-octadecynoic acid (ODYA) were without effect. The putative EDHF analogue 5,6-EET elicited constrictions in the presence of the endothelium that could be prevented by indomethacin or a TxA(2) receptor antagonist, whereas in the absence of the endothelium, EDHF elicited only small, charybdotoxin-insensitive decreases in aSM R(Ca) and dilations (max.: -8 +/- 2% and 27 +/- 4%, respectively).

CONCLUSIONS

In skeletal muscle arterioles, EDHF 1) substantially and rapidly reduces myogenic tone by decreasing aSM Ca(2+) via opening K(Ca) channels, 2) it is unlikely to be 5,6-EET or other CYP metabolites, but 3) requires functional gap junctions.

摘要

目的

研究钾离子通道、细胞色素P - 450（CYP）代谢产物5,6 -环氧二十碳三烯酸（5,6 - EET）和缝隙连接在一种非一氧化氮非前列腺素介质（称为“内皮依赖性超极化因子”（EDHF））调节骨骼肌小动脉肌源性张力中的作用，该介质由乙酰胆碱（ACh）释放产生。

方法

在离体大鼠股薄肌小动脉中，于吲哚美辛和L - 硝基精氨酸甲酯（L - NAME）存在的情况下，测量对ACh反应时平滑肌（aSM）细胞内钙离子浓度（[Ca²⁺]i，通过fura - 2比率信号变化R（Ca）评估）和直径的同步变化。

结果

ACh、钾离子ATP通道开放剂吡那地尔和钙离子通道抑制剂维拉帕米引起aSM [Ca²⁺]i类似程度的降低（最大值分别为：-32±3%、-29±3%和-30±3%）以及小动脉扩张（最大值分别为：90±4%、96±2%和95±2%）。ACh诱导的反应被氯化钾去极化、钾离子钙通道阻滞剂（四乙铵、蝎毒素）或缝隙连接抑制剂（18α - 甘草次酸、高渗蔗糖）抑制。钾离子ATP通道抑制剂格列本脲、内向整流钾通道抑制剂氯化钡或CYP抑制剂17 - 十八炔酸（ODYA）无作用。推测的EDHF类似物5,6 - EET在有内皮存在时引起收缩，吲哚美辛或血栓素A₂（TxA₂）受体拮抗剂可预防这种收缩，而在内皮不存在时，EDHF仅引起aSM R（Ca）微小的、对蝎毒素不敏感的降低和扩张（最大值分别为：-8±2%和27±4%）。