Inhibition of nitric oxide synthase produces hypothermia and
depresses lipopolysaccharide fever.
Scammell, Thomas E., Joel K. Elmquist, and Clifford B. Saper.
Department of Neurology and Program in Neuroscience, Beth Israel
Hospital and Harvard Medical School, 200 Longwood Ave., Boston,
Massachusetts 02115
APStracts 3:0071R, 1996.
The labile gas nitric oxide (NO) mediates a wide variety of
thermoregulatory processes including vasomotor control, brown fat
thermogenesis, and neuroendocrine regulation. Additionally, during
endotoxemia, NO modulates the release of cytokines and hypothalamic
peptides. To determine the role of NO in thermoregulation and fever,
we intravenously injected the NOS inhibitor NG-nitro-L-arginine
methyl ester (L-NAME) and measured it's effects on body temperature
during normal thermoregulation and endotoxemia in awake, unrestrained
rats. L-NAME produced a stereoselective, dose-dependent hypothermia
which lasted up to 4 hours after bolus intravenous injection.
Intravenous lipopolysaccharide (LPS) produced fever in a dose
-dependent manner which was preceded by hypothermia at higher doses of
LPS. NOS inhibition reduced the febrile response to LPS and produced
marked hypothermia with a low dose of LPS. These findings indicate
that NO may play an important role in thermoregulation and suggest
that NO is required for the production of fever.
Received 12 September 1995; accepted in final form 14 February
1996.
APS Manuscript Number R568-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96