Role of gap junctions in endothelium-derived hyperpolarizing factor responses and mechanisms of K+-relaxation
Role of gap junctions in endothelium-derived hyperpolarizing factor responses and mechanisms of K+-relaxation
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DOI：
10.1016/s0014-2999(00)00512-4
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发表时间：
2000-08-18
影响因子：
5
通讯作者：
Randall, MD
中科院分区：
文献类型：
--
作者：
Harris, D;Martin, PEM;Randall, MD
我们检测了哇巴因（1 mM）、差距连接抑制剂、18 α-大黄酸（100 μ M），N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺盐酸盐（SR 141716 A; 10 μ M）和棕榈油酸（50 μ M），克霉唑（10 μ M）对内皮衍生超极化因子（EDHF）介导的和K+诱导的大鼠肠系膜血管舒张。在吲哚美辛（10 μ M）和300 μ M N（G）硝基-L-精氨酸甲酯（L-NAME）存在下，卡巴胆碱引起EDHF介导的舒张（R-max = 85.3 +/- 4.0%）。在哇巴因的存在下，这些反应显著降低（R-max = 11.0 +/- 2.3%）。18 α-大黄酸、SR 141716 A、棕榈油酸和克霉唑也显著抑制这些EDHF介导的反应。K+引起用无K+缓冲液灌注的制剂的血管舒张（R-max = 73.7 +/- 2.4%），其被10 μ M吲哚美辛降低（R-max = 56.4 +/- 6.2%）。内皮剥脱基本上消除了K+血管舒张。哇巴因和18 α-大黄酸都反对K+松弛，然而，SR 141716 A，克霉唑和棕榈油酸都没有任何影响。哇巴因、克霉唑和棕榈油酸可减弱通过缝隙连接的直接细胞-细胞偶联。我们的结论是：（i）缝隙连接通讯在EDHF介导的舒张中起主要作用，（ii）K+-血管舒张是内皮依赖性的（因此，K+不太可能代表EDHF），（iii）哇巴因和克霉唑对缝隙连接的抑制作用可能有助于其对EDHF的作用。(C)2000 Elsevier Science B. V.保留所有权利。
We have examined the effects of ouabain (1 mM), the gap junction inhibitors, 18 alpha-glycyrrhetinic acid (100 mu M), N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10 mu M) and palmitoleic acid (50 mu M), and clotrimazole (10 mu M) against endothelium-derived hyperpolarizing factor (EDHF)-mediated and K+-induced vasorelaxations in the rat mesentery. In the presence of indomethacin (10 mu M) and 300-mu M N(G)nitro-L-arginine methyl ester (L-NAME), carbachol caused EDHF-mediated relaxations (R-max = 85.3 +/- 4.0%). In the presence of ouabain, these responses were substantially reduced (R-max = 11.0 +/- 2.3%). 18 alpha-glycyrrhetinic acid, SR141716A, palmitoleic acid and clotrimazole also significantly inhibited these EDHF-mediated responses. K+ caused vasorelaxation of preparations perfused with K+-free buffer (R-max = 73.7 +/- 2.4%), which were reduced by 10-mu M indomethacin (R-max = 56.4 +/- 6.2%). K+ vasorelaxation was essentially abolished by endothelial denudation. Both ouabain and 18 alpha-glycyrrhetinic acid opposed K+ relaxations, however, neither SR141716A, clotrimazole nor palmitoleic acid had any effect. Direct cell-cell coupling via gap junctions was attenuated by ouabain, clotrimazole and palmitoleic acid. We conclude that: (i) that gap junctional communication plays a major role in EDHF-mediated relaxations, (ii) that K+-vasorelaxation is endothelium-dependent (thus, K+ is unlikely to represent an EDHF), and (iii) that the inhibitory actions of ouabain and clotrimazole on gap junctions might contribute towards their effects against EDHF. (C) 2000 Elsevier Science B.V. All rights reserved.