7-NITROINDAZOLE, BUT NOT L-NAME OR AMINOGUANIDINE, ATTENUATES ANAPHYLACTIC HYPOTENSION IN CONSCIOUS RATS
7-NITROINDAZOLE, BUT NOT L-NAME OR AMINOGUANIDINE, ATTENUATES ANAPHYLACTIC HYPOTENSION IN CONSCIOUS RATS
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DOI：
10.1097/shk.0b013e31817c05bc
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发表时间：
2009-02-01
期刊：
影响因子：
3.1
通讯作者：
Kurata, Yasutaka
中科院分区：
文献类型：
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作者：
Zhang, Wei;Shibamoto, Toshishige;Kurata, Yasutaka
NO及其合酶（NOS）同工酶在未麻醉大鼠过敏性低血压中的作用尚不清楚。在卵白蛋白抗原致敏的清醒Sprague-Dawley大鼠中，分别测定了N-G-硝基-L-精氨酸甲酯（L-NAME）、氨基胍和7-硝基吲唑抑制NOS、iNOS和nNOS对抗原诱导的全身性低血压和门静脉高压的影响。直接同时测定MAP及门静脉压。对照组大鼠显示MAP沿着门静脉压升高而降低，但在抗原注射后48 h内未死亡。用非选择性NOS抑制剂L-NAME（10 mg/kg）预处理的大鼠，在抗原给药前后MAP均显著高于对照组，但MAP的净下降和门静脉压的升高均大于对照组，导致抗原给药后12 h内出现致死性结局。相反，用相对选择性nNOS抑制剂7-硝基吲唑预处理，（50 mg/kg）在抗原给药后20分钟内显着减轻了过敏性低血压，而相对选择性的iNOS抑制剂氨基胍总之，在未麻醉大鼠的过敏性低血压中，可能涉及来自nNOS的NO，而不是来自iNOS的NO，而非选择性NOS抑制剂L-NAME是致命的。
The roles of NO and isozymes of NO synthase (NOS) are not known in anaphylactic hypotension of unanesthetized rats. Effects of inhibition of NOS, iNOS, and nNOS by N-G-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and 7-nitroindazole, respectively, were determined on the antigen-induced systemic hypotension and portal hypertension in conscious Sprague-Dawley rats sensitized with the ovalbumin antigen. The MAP and portal venous pressure were directly and simultaneously measured. The control rats showed a decrease in MAP along with an increase in portal venous pressure but did not die within 48 h after antigen injection. In the rats pretreated with the nonselective NOS inhibitor L-NAME (10 mg/kg), MAP before and after antigen administration was significantly higher than that of the control rats, but the net decrease in MAP and increase in portal venous pressure were rather greater than those of the control, resulting in fatal outcome within 12 h after antigen administration. In contrast, pretreatment with the relatively selective nNOS inhibitor 7-nitroindazole (50 mg/kg) substantially attenuated anaphylactic hypotension over 20 min after antigen administration, whereas the relatively selective iNOS inhibitor aminoguanidine (100 mg/kg) did not affect it. In conclusion, in anaphylactic hypotension of unanesthetized rats, NO derived from nNOS, but not from iNOS, may be involved, and the nonselective NOS inhibitor L-NAME is lethal.