The nitric oxide pathway is an important modulator of stress-induced feverin rats

Psychological stress evokes a number of physiological responses, including a rise in body temperature (Tb), which has been suggested to be the result of an elevation in the thermoregulatory set point, i.e., a fever. This resp onse seems to share similar mechanisms with infectious fever. A growing num ber of studies have provided evidence that nitric oxide (NO) has a modulato ry role in infectious fever, but no report exists about the participation o f NO in stress fever. Thus, the present study aimed to verify the hypothesi s that NO modulates stress fever by using restraint stress as a model. To t his end, we tested the effects of the non-specific NO synthase (NOS) inhibi tor NG-nitro-L-arginine methyl ester (L-NAME) or its inactive enantiomer NG -nitro-D-arginine methyl ester (D-NAME) on colonic Tb of restrained or unre strained rats. A rapid increase in Tb was observed when animals were submit ted to restraint. Intravenous (i;v.) injection oft-NAME at a dose (10 mg/ k g) that caused no change in Tb when administered alone significantly attenu ated the elevation in Tb elicited by stress, indicating that the NO pathway may mediate stress fever. Moreover, intracerebroventricular (i.c.v.) L-NAM E (250 mug/mul) caused a rise in Tb Of euthermic animals and enhanced stres s fever, supporting that NO in the central nervous system (CNS) leads to a reduction in Tb and, therefore, this is unlikely to be the site where NO ma y mediate stress fever. Taken together, these data indicate that the NO pat hway plays an important role in modulating restraint stress-induced fever i n rats. (C) 2000 Elsevier Science Inc. All rights reserved.