Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo.
Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo.
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其心血管作用的证据表明，7-硝基吲唑可能在体内抑制内皮一氧化氮合酶。
DOI：
10.1016/0014-2999(96)00106-9
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发表时间：
1996
影响因子：
5
通讯作者：
Reiner,A
中科院分区：
文献类型：
--
作者：
Zagvazdin,Y;Sancesario,G;Wang,YX;Share,L;Fitzgerald,ME;Reiner,A
我们研究了7-硝基吲唑，据报道，神经元一氧化氮（NO）合酶的选择性抑制剂，是否诱导的心血管效应，而不抑制内皮NO合酶。在7-硝基吲唑给药（50 mg/kg i. p.）后，观察到平均动脉血压显著升高，但心率无变化。在用氨基甲酸乙酯或氨基甲酸乙酯和氯醛糖麻醉的大鼠中，而在清醒的动物中在7-硝基吲唑给药（50 mg/kg i. p.）后观察到平均动脉血压升高和心动过缓。在用较高剂量的7-硝基吲唑（75 mg/kg i. p.）处理的氯醛糖麻醉大鼠中，未观察到对平均动脉血压和心率的这些作用的增强。在乌拉坦麻醉下研究的大鼠中，使用氟烷诱导麻醉可消除7-硝基吲唑的升压作用。7-硝基吲唑可缩短乙酰胆碱（3 μg或30 μg）的作用时间。而硝普钠（2 μg i. v.）麻醉大鼠的控制性降压。用l-精氨酸（300 mg/kg i. v.）抑制7-硝基吲唑对平均动脉血压和乙酰胆碱诱导的低血压的影响，表明左旋精氨酸-NO通路参与7-硝基吲唑的作用。7-硝基吲唑对血压和对乙酰胆碱和硝普钠的降压反应的影响与以前观察到的L-精氨酸类似物非选择性NO合酶抑制后的影响相似。因此，我们的研究结果表明，7-硝基吲唑影响基础内皮NO的形成在体内。氟烷对7-硝基吲唑心血管效应的抑制作用表明，在研究NO合酶抑制剂，特别是7-硝基吲唑的心血管效应时，应考虑麻醉剂的影响。
We have examined whether the cardiovascular effects of 7-nitroindazole, a reportedly selective inhibitor of neuronal nitric oxide (NO) synthase, are induced without inhibition of endothelial NO synthase. A significant increase in mean arterial blood pressure but no change in heart rate was observed after 7-nitroindazole administration (50 mg/kg i.p.) in rats anesthetized with urethane or urethane and chloralose, while both an elevation in mean arterial blood pressure and bradycardia were observed in conscious animals after 7-nitroindazole administration (50 mg/kg i.p.). No enhancements in these effects on mean arterial blood pressure and heart rate were observed in urethane-chloralose anesthetized rats treated with a higher dose of 7-nitroindazole (75 mg/kg i.p.). Use of halothane to induce anesthesia abolished the pressor effect of 7-nitroindazole in rats studied under urethane anesthesia. 7-Nitroindazole shortened the duration of the acetylcholine (3 μg or 30 μg i.v.) but not the sodium nitroprusside (2 μg i.v.) induced hypotension in urethane-anesthetized rats. Pretreatment with l-arginine (300 mg/kg i.v.) inhibited the effects of 7-nitroindazole on mean arterial blood pressure and acetylcholine induced hypotension, suggesting involvement of the l-arginine-NO pathway in the effects of 7-nitroindazole. The effects of 7-nitroindazole on blood pressure and on the depressor responses to acetylcholine and sodium nitroprusside are similar to the effects previously observed after non-selective NO synthase inhibition by l-arginine analogs. Our results suggest, therefore, that 7-nitroindazole affects basal endothelial NO formation in vivo. The suppressive action of halothane on the cardiovascular effects of 7-nitroindazole suggests that the influence of anesthetics should be taken into consideration in studies of the cardiovascular effects of NO synthase inhibitors, particularly 7-nitroindazole.