Febrigenic signaling to the brain does not involve nitric oxide

被引:27
作者
Steiner, AA
Rudaya, AY
Ivanov, AI
Romanovsky, AA
机构
[1] St Josephs Hosp, System Inflammat Lab, Phoenix, AZ 85013 USA
[2] Med Ctr, Phoenix, AZ 85013 USA
关键词
nitrosoalbumin; nitrosoglutathione; nitrosothiols; nitric oxide synthase; L-NAME; thermoregulation; fever; lipopolysaccharide; body temperature; ambient temperature;
D O I
10.1038/sj.bjp.0705713
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase ( NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear. It is also unclear whether NOS inhibitors attenuate fever by blocking febrigenic signaling or, alternatively, by suppressing thermogenesis in brown fat. 2 Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures (T-c and T-sk) were monitored. 3 Study 1 was designed to determine whether the relatively stable, physiologically relevant forms of NO, that is, S-nitrosoalbumin (SNA) and S-nitrosoglutathione (SNG), are pyrogenic and whether they enhance LPS fever. At a neutral ambient temperature (T-a) of 31degreesC, afebrile or LPS (1 mug kg(-1), i.v.)-treated rats were infused i.v. with SNA (0.34 or 4.1 mumol kg(-1); the controls received NaNO2 and albumin) or SNG (10 or 60 mumol kg(-1); the controls received glutathione). T-c of SNA- or SNG-treated rats never exceeded that of the controls. 4 In Study 2, we tested whether the known fever-attenuating effect of the NOS inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) at a subneutral T-a (when fever is brought about by thermogenesis) also occurs at a neutral Ta (when fever is brought about by skin vasoconstriction). At a subneutral T-a of 24degreesC, L-NAME (2.5 mg kg(-1), i.v.) attenuated LPS (10 mug kg(-1), i.v.) fever, presumably by inhibiting thermogenesis. At 31degreesC, L-NAME enhanced LPS fever by augmenting skin vasoconstriction (T-sk fall). 5 In summary, both SNA and SNG had no pyrogenic effect of their own and failed to enhance LPS fever; peripheral L-NAME attenuated only fever brought about by increased thermogenesis. It is concluded that NO is uninvolved in febrigenic signaling to the brain.
引用
收藏
页码:1204 / 1213
页数:10
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