Nitric oxide synthase inhibitors, 7-nitro indazole and nitroG-L-arginine methyl ester, dose dependently reduce the threshold for isoflurane anesthesia.
Nitric oxide synthase inhibitors, 7-nitro indazole and nitroG-L-arginine methyl ester, dose dependently reduce the threshold for isoflurane anesthesia.
复制标题
一氧化氮合酶抑制剂、7-硝基吲唑和硝基G-L-精氨酸甲酯，剂量依赖性地降低异氟醚麻醉阈值。
DOI：
10.1097/00000542-199611000-00020
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发表时间：
1996
期刊：
影响因子：
8.8
通讯作者：
Johns,RA
中科院分区：
文献类型：
--
作者：
Pajewski,TN;DiFazio,CA;Moscicki,JC;Johns,RA
BackgroundNitric oxide (NO), a recognized cell messenger for activating soluble guanylate cyclase, is produced by the enzyme NO synthase in a wide variety of tissues, including vascular endothelium and the central nervous system. The authors previously reported the possible involvement of the NO pathway in the anesthetic state by showing that a specific NO synthase inhibitor, nitroG-L-arginine methyl ester (L-NAME), dose dependently and reversibly decreases the minimum alveolar concentration (MAC) for halothane anesthesia. The availability of a structurally distinct inhibitor selective for the neuronal isoform of NO synthase, 7-nitro indazole (7-NI), allowed for the possibility of dissociating the central nervous system effects of neuronal NO synthase inhibition from the cardiovascular effects of endothelial NO synthase inhibition.MethodsThe effect of two structurally distinct inhibitors of NO synthase, L-NAME and 7-NI, on the MAC of isoflurane was investigated in Sprague-Dawley rats while concurrently monitoring the animals' arterial blood pressure and heart rate. L-NAME (1 to 30 mg/kg given intravenously, dissolved in 0.9% saline) and 7-NI (20 to 1,000 mg/kg given intraperitoneally, dissolved in arachis oil) were administered after determining control MAC and 30 min before determining MAC in the presence of NO synthase inhibitor.ResultsL-NAME and 7-NI caused a dose-dependent decrease from isoflurane control MAC (maximal effect: 35.5+/-2.5% and 43.0+/-1.7%, respectively) with a ceiling effect observed for both NO synthase inhibitors (above 10 mg/kg and 120 mg/kg, respectively). L-NAME administration significantly increased systolic and diastolic blood pressures (maximal effect: 39.9+/-2.2% and 64.3+/-4.0%, respectively), which were not accompanied by any changes in heart rate. 7-NI administration resulted in no changes in blood pressure and a small but clinically insignificant decrease in heart rate.ConclusionsInhibition of the NO synthase pathway decreased the MAC for isoflurane, which suggests that inhibition of the NO pathway decreases the level of consciousness and augments sedation, analgesia, and anesthesia. The MAC reduction by two structurally distinct NO synthase inhibitors supports that this is a specific effect on NO synthase. Furthermore, the action of the neuronal NO synthase inhibitor 7-NI supports an effect selective for neuronal NO synthase and also avoids the hypertensive response of generalized NO synthase inhibitors.
