Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine.
Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine.
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视前一氧化氮通过抑制去甲肾上腺素的 POA 释放来减轻豚鼠的内毒素发热。
DOI：
10.1152/ajpregu.00068.2007
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Blatteis,ClarkM
中科院分区：
文献类型：
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作者：
Feleder,Carlos;Perlik,Vit;Blatteis,ClarkM
脂多糖（LPS）诱导下丘脑一氧化氮（NO）；NO对视前区（POA）有解热作用，但其作用机制尚不清楚。LPS还刺激视前去甲肾上腺素（NE）的释放，NE介导发热。由于NE上调NO合成酶，而NO诱导环氧化酶(COX)-2依赖性PGE2，我们研究了NO是否介导这种中枢热介质的产生。使用poa微透析探针的有意识豚鼠静脉注射LPS (2 μg/kg)，然后静脉注射NO供体（SIN-1）或清除剂（羧基ptio） poa（各20 μg/μl， 2 μl/min, 6 h）。持续监测堆芯温度（Tc）；透析液NE和pge2在收集30分钟后进行分析。为了验证α2-肾上腺素受体（AR）参与pge2生成的报道，我们用SIN-1或羧基ptio对可乐定（α2-AR激动剂，2 μg/μl）进行微透析。为了评估氧化NE和/或NO产物在初步证明的cox -2非依赖性POA PGE2增加中的可能参与，(+)-儿茶素（一种抗氧化剂，3 μg/μl）进行了微透析，并测定了POA PGE2和tc2。SIN-1和羧基ptio分别降低和增强静脉注射LPS产生的NE、PGE2和tc3的升高。同样，它们分别阻止和增加pge2的延迟升高和poa内可乐定诱导的延迟升高。（+）-儿茶素能抑制lps诱导的PGE2升高，但不能抑制Tc升高。我们得出结论，NO的解热活性源于其抑制lps诱导的POA NE的释放。这些数据也暗示自由基参与POA pge2的产生，并对其作为中枢性LPS发热介质的作用提出了疑问。
Lipopolysaccharide (LPS) administration induces hypothalamic nitric oxide (NO); NO is antipyretic in the preoptic area (POA), but its mechanism of action is uncertain. LPS also stimulates the release of preoptic norepinephrine (NE), which mediates fever onset. Because NE upregulates NO synthases and NO induces cyclooxygenase (COX)-2-dependent PGE2, we investigated whether NO mediates the production of this central fever mediator. Conscious guinea pigs with intra-POA microdialysis probes received LPS intravenously (2 μg/kg) and, thereafter, an NO donor (SIN-1) or scavenger (carboxy-PTIO) intra-POA (20 μg/μl each, 2 μl/min, 6 h). Core temperature (Tc) was monitored constantly; dialysate NE and PGE2were analyzed in 30-min collections. To verify the reported involvement of α2-adrenoceptors (AR) in PGE2production, clonidine (α2-AR agonist, 2 μg/μl) was microdialyzed with and without SIN-1 or carboxy-PTIO. To assess the possible involvement of oxidative NE and/or NO products in the demonstrated initially COX-2-independent POA PGE2increase, (+)-catechin (an antioxidant, 3 μg/μl) was microdialyzed, and POA PGE2, and Tcwere determined. SIN-1 and carboxy-PTIO reduced and enhanced, respectively, the rises in NE, PGE2, and Tcproduced by intravenous LPS. Similarly, they prevented and increased, respectively, the delayed elevations of PGE2and Tcinduced by intra-POA clonidine. (+)-Catechin prevented the LPS-induced elevation of PGE2, but not of Tc. We conclude that the antipyretic activity of NO derives from its inhibitory modulation of the LPS-induced release of POA NE. These data also implicate free radicals in POA PGE2production and raise questions about its role as a central LPS fever mediator.