Mechanisms of hydrogen-peroxide-induced biphasic response in rat mesenteric artery
Mechanisms of hydrogen-peroxide-induced biphasic response in rat mesenteric artery
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DOI：
10.1038/sj.bjp.0705147
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发表时间：
2003-03-01
影响因子：
7.3
通讯作者：
Lee, RMKW
中科院分区：
文献类型：
--
作者：
Gao, YJ;Hirota, S;Lee, RMKW
1.在苯肾上腺素（PHE）（1 μ M）预收缩的成年大鼠上级肠系膜动脉中，低浓度的过氧化氢（H2 O2，10-100 μ M）仅引起收缩，而高浓度的H2 O2（0.3-1 μ M）引起双相反应：短暂收缩，随后是舒张反应。2去除内皮素不影响双相反应。7，7-二甲基-（5 Z，8 Z）-二十碳二烯酸、双氯芬酸、呋替酯或SQ 29548极大地抑制收缩，但不影响舒张。17-十八炔酸、二十碳三炔酸、ICI 198615、SQ 22536或ODQ不抑制双相反应。3 40 mm处的KCl抑制对H2 O2的舒张反应达98 ± 24%。4-氨基吡啶（4-AP）抑制，而四乙基氯化铵（TEA），Charybdotoxin，或格列本脲减弱舒张反应。4-AP、TEA和格列本脲的组合模拟了40 mm KCl的作用。伊比利亚毒素，蜂毒肽，或氯化钡没有抑制舒张反应。4 H2 O2在I毫米超极化膜电位和可逆性增强的K+电流在肠系膜动脉平滑肌细胞。总之，在PHE预收缩的大鼠肠系膜动脉中：（1）当H_2O_2增加到0.3mm或更高时，对H_2O_2的反应从收缩定性地转变为双相反应：（2）舒张反应是由K ~+通道激活引起的，其中电压依赖性K ~+通道起主要作用;（3）H_2O_2对K ~+通道的激活不依赖于磷脂酶A_2、环氧合酶、脂氧合酶、细胞色素P450单加氧酶、腺苷酸或鸟苷酸环化酶。英国药理学杂志（2003）138，1085-1092。doi：10.1038/sj.bjp.705147。
1. In phenylephrine (PHE) (1 muM)-precontracted superior mesenteric arteries from adult rats, low concentration of hydrogen peroxide (H2O2, 10-100 muM) caused only contraction, while high concentration of H2O2 (0.3-1 mm) caused a biphasic response: a transient contraction followed by a relaxation response.2 Endothelium removal did not affect the biphasic response. 7,7-Dimethyl-(5Z,8Z)-eicosadienoic acid, diclofenac, furegrelate, or SQ 29548 greatly inhibited the contraction but did not affect the relaxation. 17-Octadecynoic acid, eicosatriynoic acid, ICI 198615, SQ 22536, or ODQ did not inhibit the biphasic response.3 KCl at 40mm inhibited the relaxation response to H2O2 by 98+24%. 4-Aminopyridine (4-AP) inhibited while tetraethylammonium chloride (TEA), charybdotoxin, or glibenclamide attenuated the relaxation response. A combination of 4-AP, TEA and glibenclamide mimicked the effects of 40mm KCl. Iberiotoxin, apamin, or barium chloride did not inhibit the relaxation response.4 H2O2 at I mm hyperpolarized membrane potential and reversibly augmented K+ current in smooth muscle cells of mesenteric artery. These effects of H2O2 were attenuated significantly by 4-AP.5 In summary, in PHE-precontracted rat mesenteric artery: (1) the response to H2O2 shifted qualitatively from contraction to a biphasic response as H2O2 increased to 0.3 mm or higher; (2) the relaxation response is caused by the activation of K+ channels, with voltage-dependent K+ channels playing a primary role; and the contraction is likely to be mediated by thromboxane A(2); (3) the K+ channel activation by H2O2 is independent of phospholipase A2, cyclooxygenase, lipoxygenase, cytochrome P450 monooxygenase, adenylate or guanylate cyclase. British Journal of Pharmacology (2003) 138, 1085-1092. doi: 10.1038/sj.bjp.705147.