The effect of central angiotensin AT 1-receptor blockade on thermoregulation in rats during exercise on a treadmill (18 m/min, 5% inclination) was investigated. Core (T b) and skin tail temperatures were measured in rats while they were exercising until fatigue after injection of 2 l of losartan (Los; 20 nmol, n ϭ 4; 30 nmol, n ϭ 4; 60 nmol, n ϭ 7), an angiotensin II AT 1-receptor antagonist, or 2 l of 0.15 mol/l NaCl (Sal; n ϭ 15) into the right lateral cerebral ventricle. Body heat rate (BHR), heat storage rate, threshold Tb for tail vasodilation (TTbV), time to fatigue, and workload were calculated. During exercise, the BHR and heat storage rate of Los-treated animals were, respectively, 40 and 53% higher (P Ͻ 0.01) than in Sal-treated animals. Additionally, rats injected with Los showed an increased TTbV (38.59 Ϯ 0.19°C for Los vs. 38.12 Ϯ 0.1°C for Sal, P Ͻ 0.02), a higher Tb at fatigue point (39.07 Ϯ 0.14°C Los vs. 38.66 Ϯ 0.07°C Sal, P Ͻ 0.01), and a reduced running performance (27.29 Ϯ 4.48 min Los vs. 52.47 Ϯ 6.67 min Sal, P Ͻ 0.01), which was closely related to the increased BHR. Our data suggest that AT1-receptor blockade attenuates heat dissipation during exercise due to the higher TTbV, leading to a faster exercise-induced increase in Tb, thus decreasing running performance. tail vasodilation; fatigue; heat balance ACTING CENTRALLY, ANGIOTENSIN II (ANG II), exerts thermoregulatory effects characterized by a decreased metabolic rate, a fall in core temperature (T b ), and an increase in tail skin temperature (T tail ) (43,44,46), through angiotensin type 1 (AT 1 ) receptors. These receptors are widely spread through the central nervous system (CNS), including the preoptic area/ anterior hypothalamus (POA/AH), regions of the hypothalamus considered to be the integrative centers of body temperature (5,29,34,35). In addition, the subfornical organ (SFO) is critical for the central actions of ANG II (8, 14). The AT 1 -receptor antagonist losartan (Los) has been used to investigate the role of ANG II in T b . Some studies have observed that intracerebroventricular (icv) injection of Los inhibited the hypothermic effect of ANG II, producing an increase in T b of resting animals exposed to a hot environment (7,27). In addition, Horowitz and colleagues (17,36) showed that central administration of Los elevates the temperature threshold for peripheral vasodilation and causes a downward shift in the threshold for evaporative cooling during heat stress, indicating the involvement of hypothalamic angiotensinergic signaling in thermoregulation. Because hypothermia and increased heat dissipation may be neuroprotective, activation of central angiotensinergic transmission may exert important effects on thermoregulation during exercise, influencing running performance.Elevated internal body temperature and increased heat storage (9, 12, 30) have been considered to be limiting factors that reduce the CNS drive for exercise performance (31,32,40) and precipitate feelings of fatigue, thus protecting the brain from ther...