Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium
Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium
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DOI：
10.1152/ajpheart.1999.276.3.h1107
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发表时间：
1999-03-01
影响因子：
4.8
通讯作者：
Langton, PD
中科院分区：
文献类型：
--
作者：
Doughty, JM;Plane, F;Langton, PD
在大鼠肠系膜动脉中，内皮源性超极化因子（EDHF）被维生素a和肉毒毒素（ChTX）联合阻断。这些毒素的作用部位尚未确定。我们比较了选择性应用ChTX和apamin对内皮和平滑肌的影响。在等距安装的动脉中，ACh (0.01-10 μ m)，吲哚美辛（2.8 μ m）和nw -硝基- l -精氨酸甲酯（L-NAME） （100 μ m）存在时，浓度依赖性放松的苯肾上腺素（PE）刺激张力（EC50 50 nM; n = 10）。Apamin （50 nM）和ChTX （50 nM）消除了这种松弛（n = 5）。在受压动脉中，在吲哚美辛（2.8 μ M）和L-NAME （100 μ M）存在的情况下，腔内应用ACh (10 μ M)，扩张pe刺激（0.3-0.5 μ M, n = 5）和肌原性张力（n = 3）。腹腔内应用Apamin （50 nM）和ChTX （50 nM）可消除乙酰胆碱诱导的扩张。apamin和ChTX的超灌注不影响ach诱导的pe刺激的扩张（n = 5）或肌原性张力（n = 3）。这是首次证明ChTX和apamin选择性地作用于内皮细胞以阻断edhf介导的松弛。
In rat mesenteric artery, endothelium-derived hyperpolarizing factor (EDHF) is blocked by a combination of apamin and charybdotoxin (ChTX). The site of action of these toxins has not been established. We compared the effects of ChTX and apamin applied selectively to the endothelium and to the smooth muscle. In isometrically mounted arteries, ACh (0.01-10 mu m), in the presence of indomethacin (2.8 mu M) and Nw-nitro-L-arginine methyl ester (L-NAME) (100 mu M), concentration dependently relaxed phenylephrine (PE)-stimulated tone (EC50 50 nM; n = 10). Apamin (50 nM) and ChTX (50 nM) abolished this relaxation (n = 5). In pressurized arteries, ACh (10 mu M), applied intraluminally in the presence of indomethacin (2.8 mu M) and L-NAME (100 mu M), dilated both PE-stimulated (0.3-0.5 mu M; n = 5) and myogenic tone (n = 3). Apamin (50 nM) and ChTX (50 nM) applied intraluminally abolished ACh-induced dilatations. Bath superperfusion of apamin and ChTX did not affect ACh-induced dilatations of either PE-stimulated (n = 5) or myogenic tone (n = 3). This is the first demonstration that ChTX and apamin act selectively on the endothelium to block EDHF-mediated relaxation.