Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats
Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats
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DOI：
10.1038/sj.bjp.0705433
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发表时间：
2003-09-01
影响因子：
7.3
通讯作者：
Kawai, K
中科院分区：
文献类型：
--
作者：
Kawabata, A;Nakaya, Y;Kawai, K
1蛋白水解酶激活受体-2(PAR-2)激动剂在体内引起低血压和胃粘膜血流量(GMBF)增加。因此，我们在体内研究了PAR-2激活对循环的调节机制，特别是与内皮源性超极化因子(EDHF)的参与有关。2测定了麻醉大鼠的动脉血压和GMBF。3静脉注射PAR-2激活肽SLIGRL-NH2和/或胰酶可使大鼠胃粘膜血管阻力(GMVR)降低，GMBF增加，GMBF增加。4阿帕明和查氏毒素联合应用，但不是单独使用，可特异性地消除PAR-2激动剂引起的降压，增加GMBF，降低GMVR。5在分离的大鼠胃动脉上，SLIGRL-NH2即使在NO合成酶抑制剂和吲哚美辛存在的情况下，也能引起内皮依赖性的松弛6我们的数据表明，在PAR-2触发的低血压和GMBF增加过程中，阿帕明/碳钼毒素敏感的K+通道参与其中，这预示着EDHF样因子的作用。
1 Agonists for protease-activated receptor-2(PAR-2) cause hypotension and an increase in gastric mucosal blood flow (GMBF) in vivo. We thus studied the mechanisms underlying the circulatory modulation by PAR-2 activation in vivo, especially with respect to involvement of endothelium-derived hyperpolarizing factor (EDHF).2 Arterial blood pressure and GMBF were measured in anesthetized rats in vivo. Vascular relaxation was assessed in the precontracted rat gastric arterial rings in vitro.3 The PAR-2-activating peptide SLIGRL-NH2 and/or trypsin, administered i.v., produced largely NO-independent hypotension and increase in GMBF accompanied by decreased gastric mucosal vascular resistance (GMVR) in rats.4 Combined administration of apamin and charybdotoxin, but not each of them, specifically abolished the hypotension, increased GMBF and decreased GMVR caused by the PAR-2 agonists.5 In the isolated rat gastric artery, SLIGRL-NH2 elicited endothelium-dependent relaxation even in the presence of an NO synthase inhibitor and indomethacin, which was abolished by apamin plus charybdotoxin.6 Our data suggest involvement of apamin/charybdotoxin-sensitive K+ channels in the PAR-2-triggered hypotension and increased GMBF, predicting a role of EDHF-like factors.