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Febrigenic signaling to the brain does not involve nitric oxide
Author(s) -
Steiner Alexandre A,
Rudaya Alla Y,
Ivanov Andrei I,
Romanovsky Andrej A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705713
Subject(s) - nitric oxide , nitric oxide synthase , thermogenesis , lipopolysaccharide , thermoregulation , endocrinology , vasoconstriction , medicine , chemistry , pharmacology , adipose tissue
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. Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures ( T c and T sk ) were monitored.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 31°C, afebrile or LPS (1 μ g kg −1 , i.v.)‐treated rats were infused i.v. with SNA (0.34 or 4.1 μ mol kg −1 ; the controls received NaNO 2 and albumin) or SNG (10 or 60 μ mol kg −1 ; the controls received glutathione). T c of SNA‐ or SNG‐treated rats never exceeded that of the controls. In Study 2 , we tested whether the known fever‐attenuating effect of the NOS inhibitor N ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) at a subneutral T a (when fever is brought about by thermogenesis) also occurs at a neutral T a (when fever is brought about by skin vasoconstriction). At a subneutral T a of 24°C, L ‐NAME (2.5 mg kg −1 , i.v.) attenuated LPS (10 μ g kg −1 , i.v.) fever, presumably by inhibiting thermogenesis. At 31°C, L ‐NAME enhanced LPS fever by augmenting skin vasoconstriction ( T sk fall). 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.British Journal of Pharmacology (2004) 141 , 1204–1213. doi: 10.1038/sj.bjp.0705713