Central angiotensin AT₁-receptor blockade affects thermoregulation and running performance in rats

Abstract

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...

The Involvement of Brain Monoamines in the Onset of Hyperthermic Central Fatigue

“…This detail allows for the possibility that reaching a critically high body temperature by itself may not be the main factor in predicting fatigue. In fact, this result is in agreement with the concept that dynamic variables strongly contribute to the reduction of physical performance Hasegawa et al, 2008;Lacerda et al, 2005Lacerda et al, , 2006Leite et al, 2006, L. O. Rodrigues et al, 2003A. G. Rodrigues et al, 2004Soares et al, 2004Soares et al, , 2007Wanner et al, 2007).…”

“…An elevation in internal body temperature and an increase in heat storage have been proposed as limiting factors to physical performance. Recent data support the hypothesis that both the heat storage rate and the internal body temperature seem to be the important determinants of fatigue during exercise (Balthazar et al, 2010;Coelho et al, 2010;Garcia et al, 2006;Lacerda et al, 2005;Leite et al, 2006;Magalhães et al, 2010;Nassif et al, 2008;A. G. Rodrigues et al, 2008;Soares et al, 2004Soares et al, , 2007.…”

“…Even though it has been stated that central fatigue coincides with the attainment of fixed high body and brain temperatures (Fuller et al, 1998;Gonzalez-Alonso et al, 1999;Nielsen et al, 1993;Walters et al, 2000), there is evidence that dynamic mechanisms are consistent regulators of feelings of fatigue. In support of this hypothesis, the rates of heat storage and body heating that are associated with changes in neurotransmitter content in thermoregulatory centers emerge as important factors in determining fatigue Hasegawa et al, 2008;Lacerda et al, 2005Lacerda et al, , 2006Leite et al, 2006, L. O. Rodrigues et al, 2003A. G. Rodrigues et al, 2004Soares et al, 2004Soares et al, , 2007Wanner et al, 2007).…”

“…G. Rodrigues et al, 2004Soares et al, 2004Soares et al, , 2007Wanner et al, 2007). There are many findings that differ from the hypothesis that fatigue is predicted by a defined high body temperature Hasegawa et al, 2008;Lacerda et al, 2005Lacerda et al, , 2006Leite et al, 2006, L. O. Rodrigues et al, 2003A. G. Rodrigues et al, 2004Soares et al, 2004Soares et al, , 2007Wanner et al, 2007).…”

“…M. Wilson & Fregly, 1985).Central treatment with losartan (angiotensin II AT 1 receptor antagonist) worsens hyperthermia and increases the body heating rate and heat storage rate that are indirectly related to the time to fatigue. This hyperthermic response is due to a heat imbalance that is characterized by higher heat production and lower peripheral heat loss (Leite et al, 2006(Leite et al, , 2007. These effects of angiotensin II on heat balance during exercise were shown to be linked to serotonergic pathways .…”