APPS November 2002 Meeting Abstract 1127

The neurotransmitter nitric oxide (NO) is implicated in central thermoregulatory control because it enhances heat defence mechanisms^1,2. This study aimed to elucidate the role of NO in thermoregulation during heat stress and at room temperature using nitric oxide synthase (NOS) inhibition. Treatment with the NOS-inhibitor N-Nitro-L-Arginine methyl ester (L-NAME) (0.3mg, intracerebroventricularly (ICV)) to male Sprague-Dawley rats (n=8) resulted in an augmented rise core temperature (T_c) during 60 minutes of exposure 39ËšC compared with the administration of artificial cerebrospinal fluid (aCSF). T_c in L-NAME-treated animals (41.6°C ±0.3) was higher (p=0.017) than aCSF-treated animals (40.8°C ±0.1) at the midpoint of heat stress, and many L-NAME-treated animals reached the 42ËšC experimental cut-off before the protocol was complete. Tail-skin temperatures (T_s) were not different between groups. Subsequent investigations into the effect of central L-NAME administration at room temperature revealed that ICV L-NAME elevated T_c (by 1.7°C at 3 hours, p<0.001) and decreased T_s (by 2.8°C at 3 hours, p<0.001), suggesting a coordinated central heat-conserving effect when NOS is inhibited. To control for possible systemic effects, we administered L-NAME (0.3mg) via the tail vein. Peripheral L-NAME at this dose caused no difference in body temperature. We conclude that there is a central nitrergic mechanism responsible for the maintenance of normal body temperature which when blocked, causes T_c to increase independently of cutaneous vasoconstriction, possibly through increased heat generation in the brown adipose tissue.