To assess the role of nitric oxide (NO) in central thermoregulatory mechanisms during exercise. 1.43 mu mol (2 mu L) of N-omega-nitro-L-arginine methyl ester (L-NAME, n = 6), a NO synthase inhibitor, or 2 mu L of 0.15 M NaCl (SAL, n = 6) was injected into the lateral cerebral ventricle of male Wistar rats immediately before the animals started running (18 m min (1). 5% inclination). Core (T-b) and skin tail (T-tnt) temperatures were measured. Body heating rate (BHR), threshold T-b for tail vasodilation (TTbV), and workload (W) were calculated. During the first 11 min of exercise, there was a greater increase in T-b in the L-NAME group than in the SAL group (BRH = 0.17 +/- 0.02 C min (1). t-NAME. versus 0.09 +/- 0.01 degrees C min(-1), SAL, p < 0.05). Following the first 11 min until similar to 40 min of exercise. T-b, levels remained stable in both groups, but levels remained higher in the L-NAME group than in the SAL group (39.16 +/- 0.04 C, L-NAME, versus 38.33 0,02 C.SAL,p < 0.01),However, exercise went on to induce an additional rise in T-b in the SAL group prior to fatigue, These results suggest that the reduced W observed in L-NAME-treated rats (10.8 +/- 2.01 kg m. L-NAME. versus 25.0 +/- 2.1 kg m, SAL, p < 0,01) was related to the increased BHR in L-NAME-treated animals observed during the first 11 min of exercise (r = 0.74.p < 0.01) due to the change in TTbV (39.12 +/- 0.24 C. L-NAME. versus 38.27 +/- 0.10 degrees C, SAL, p < 0.05). Finally, our data suggest that the central nitric oxide pathway modulates mechanisms of heat dissipation during exercise through an inhibitory mechanism. (D 2005 Elsevier Inc. All rights reserved.