APPS November 2002 Meeting Abstract 1127


Imogen Arnold1,2 , M.J. McKinley1 , M.A. Febbraio3, M.L. Mathai1, 1 Howard Florey Institute, Vic, 2 Department of Physiology, University of Melbourne, Vic, 3 School of Medical Sciences, RMIT University, Vic.

The neurotransmitter nitric oxide (NO) is implicated in central thermoregulatory control because it enhances heat defence mechanisms1,2. 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 (Tc) during 60 minutes of exposure 39˚C compared with the administration of artificial cerebrospinal fluid (aCSF). Tc in L-NAME-treated animals (41.6C 0.3) was higher (p=0.017) than aCSF-treated animals (40.8C 0.1) at the midpoint of heat stress, and many L-NAME-treated animals reached the 42˚C experimental cut-off before the protocol was complete. Tail-skin temperatures (Ts) were not different between groups. Subsequent investigations into the effect of central L-NAME administration at room temperature revealed that ICV L-NAME elevated Tc (by 1.7C at 3 hours, p<0.001) and decreased Ts (by 2.8C 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 Tc to increase independently of cutaneous vasoconstriction, possibly through increased heat generation in the brown adipose tissue.

(1) Eriksson, S., et al., Brain Research. 1997.

(2) Mathai, M.L., et al., American Journal of Physiology. 1997.

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