Role of nitric oxide in 2-deoxy-D-glucose-induced hypothermia in rats

Abstract

The present study was designed to test the hypothesis that nitric oxide (NO) plays a role in 2-deoxy-D-glucose (2-DG)-induced hypothermia. The body temperature of awake, unrestrained rats was measured before and after the administration of 2-DG, or N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor) or both treatments together. We observed a significant reduction in body temperature after 2-DG injection. L-NAME alone caused no significant change in body temperature. When the two treatments were combined, a reduction in the magnitude of 2-DG-induced hypothermia was observed. The neuronal NOS inhibitor 7-nitroindazole also inhibited 2-DG-induced hypothermia. The data indicate that NO, probably produced by neuronal NOS, plays a role in 2-DG-induced hypothermia.

Role of neuronal nitric oxide synthase in hypoxia-induced anapyrexia in rats

“…A route mediating the reduction in T c may be the impairment of central oxidative phosphorylation, because intracerebroventricular injection of inhibitors of oxidative phosphorylation, such as azide or cyanide, reduces the preferred body temperature of toads (9). Moreover, exclusion of glucose from central sites plays a major role in hypoglycemia-induced hypothermia (7,11). Taken together, these data indicate that the role of the central nervous system in body temperature control is subject to numerous modifiers, including NO.…”

“…Actually, NO has been shown to play an important role in nonshivering thermogenesis by acting on brown adipose tissue (32) and may be important for shivering thermogenesis as it may increase contractile function (24,30,31). On the other hand, nNOS inhibition in the central nervous system could also alter T c , but this is unlikely to contribute to the hypothermic effect of 7-NI at 30 mg/kg because NO in the central nervous system seems to be an antipyretic molecule (1,19) and seems to mediate anapyrexia (5,8,11,37). However, it is important to point out that NO may also be pyretic in some brain regions (21).…”

“…In the present study, we were unable to centrally administer 7-NI because it requires an oil vehicle and therefore it was impossible to identify the site of nNOS action. However, because the nNOS isoform has been found in the periphery at the thermogenic tissues (sympathetic ganglia of brown adipose tissue and skeletal muscle; 24,25,36), whereas NO in the central nervous system has been shown to mediate hypothermic stimuli such as hypoxia (8), systemic AVP (37), and 2-deoxy-D-glucose (11), it is likely that 7-NI attenuates hypoxia-induced anapyrexia by inhibiting NO synthesis by nNOS in the central nervous system. Yet, supporting the effect of NO reducing T c by acting on the central nervous system, experiments performed on febrile animals also demonstrated that intracerebroventricular administration of NO donors elicits antipyresis, whereas intracerebroventricular L-NAME enhances fever (1,19).…”

Role of the hypothalamus in mediating protective effects of dietary restriction during aging

“…Similarly, hypoglycemia and glucopenia can reduce body temperature in humans [60, 140] and other species [169] [20, 31, 153]. Reducing temperature dramatically increases lifespan in poikilothermic (cold-blooded) animals [40, 84, 112–116, 206, 220] but the effect in mammals has been challenging to determine.…”

Central dopamine modulates anapyrexia but not hyperventilation induced by hypoxia

“…In fact, recent data indicate that the role of the CNS in thermoregulation during hypoxia is subjected to numerous modifiers, such as adenosine (14), lactate (29), and opioids (14). Among them, nitric oxide seems to be a proximal mediator of several anapyretic stimuli (5,7), which may suggest a common final pathway.…”