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Febrigenic signaling to the brain does not involve nitric oxide
Alexandre A Steiner1, Alla Y Rudaya, Andrei I Ivanov
1Systemic Inflammation Laboratory, Trauma Research, St Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USA.
British Journal of Pharmacology
|March 10, 2004
Summary
Peripheral nitric oxide (NO) does not signal to the brain to cause fever. Studies show stable NO forms do not trigger fever, and NO synthase inhibitors only affect fever related to thermogenesis, not brain signaling.
Area of Science:
- Physiology
- Neuroscience
- Pharmacology
Background:
- Peripheral nitric oxide (NO) involvement in fever signaling to the brain is hypothesized.
- NO synthase (NOS) inhibitors reduce lipopolysaccharide (LPS)-induced fever in rodents.
- Mechanisms of NO action in fever, including febrigenic signaling and thermogenesis, remain unclear.
Purpose of the Study:
- To investigate if stable NO forms (SNA, SNG) are pyrogenic or enhance LPS fever.
- To determine if NOS inhibition affects fever at neutral versus subneutral ambient temperatures.
- To clarify NO's role in febrigenic signaling versus thermogenesis during fever.
Main Methods:
- Male Wistar rats with jugular catheters monitored for colonic and tail skin temperatures.
- Intravenous infusion of S-nitrosoalbumin (SNA) or S-nitrosoglutathione (SNG) in afebrile or LPS-treated rats.
- Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) at neutral (31°C) and subneutral (24°C) ambient temperatures.
Main Results:
- SNA and SNG were not pyrogenic and did not enhance LPS-induced fever.
- L-NAME attenuated LPS fever at 24°C, likely by inhibiting thermogenesis.
- At 31°C, L-NAME augmented LPS fever by increasing skin vasoconstriction.
Conclusions:
- Stable NO forms do not trigger fever.
- Peripheral NO is not involved in febrigenic signaling to the brain.
- NOS inhibitors impact fever primarily through thermogenesis modulation, not central signaling.