Inhibitors of nitric oxide synthesis block cold-induced thermogenesis in rats

Kamerman, Peter R.; Laburn, Helen P.; Mitchell, Duncan

doi:10.1139/y03-069

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…A similar effect was described in rats exposed to hypoxia at low Tb, showing a greater hypometabolic response when compared with the change in V E (34). The decreases in VO 2 and Tb observed after NOS blockade in this study are also supported by previous studies in rats that have shown that NO mediates thermogenesis in mammals (35,36).…”

Section: Discussionsupporting

confidence: 89%

Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide

2007

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Administration of Escherichia coli endotoxin attenuates the ventilatory response to hypoxia (VRH) in newborn piglets, but the mechanisms responsible for this depression are not clearly understood. Nitric oxide (NO) production increases during sepsis and elevated NO levels can inhibit carotid body function. The role of endothelial NO on the VRH during endotoxemia was evaluated in 26 young rats. Minute ventilation (V E ) and oxygen consumption (VO 2 ) were measured in room air (RA) and during 30 min of hypoxia (10% O 2 ) before and after E. coli endotoxin administration. During endotoxemia, animals received placebo (PL, n ϭ 8); a nonselective nitric oxide synthase (NOS) inhibitor (N G -nitro-L-arginine methyl ester, L-NAME, n ϭ 9), or a neuronal NOS (nNOS) inhibitor (7-nitroindazole, 7-NI, n ϭ 9). During endotoxemia, a larger increase in V E was observed only during the first min of hypoxia in the L-NAME group when compared with PL or 7-NI (p Ͻ 0.001). VRH was similar in the PL and 7-NI groups. A larger decrease in VO 2 at 30 min of hypoxia was observed in L-NAME and 7-NI groups when compared with PL (p Ͻ 0.03). These data demonstrate that the attenuation of the early VRH during endotoxemia is in part mediated by an inhibitory effect of endothelial NO on the respiratory control mechanisms. (Pediatr Res 62: 134-138, 2007) C hanges in breathing pattern and apnea episodes are frequently observed in newborns and infants with sepsis (1). In adult humans, endotoxin administration results in changes in the basal respiratory pattern and dyspnea (2). We previously demonstrated that endotoxin infusion in newborn piglets produced attenuation of the VRH (3). In a pilot study, we also observed similar respiratory behavior in 4-to 6-wkold rats. The interaction of hypoxia, infection, and cytokine abnormalities has been suggested as a possible mechanism of sudden infant death syndrome (SIDS) (4).The mechanisms that explain the changes in breathing pattern during sepsis are not clearly understood. Respiratory muscle fatigue or alterations in lung mechanics and metabolic rate have been associated with the respiratory changes observed during Gram-positive and negative septicemia in piglets (3,5,6). Particularly, the attenuation in the VRH observed after endotoxin administration to unanesthetized newborn piglets was associated with a significant decrease in VO 2 (3). Sepsis can induce the release of inflammatory mediators such as cytokines; prostaglandins, and NO (7,8), which may be responsible for the alterations of the breathing pattern observed during endotoxemia and also may be an important component of many deaths attributed to SIDS (4).It is known that NO is an active participant in the pathophysiology of endotoxemia (9). NO is synthesized from Larginine by three different isoenzymes of NOS: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) (10). Increased eNOS activation and endothelial NO release have been observed shortly after endotoxin administration (11,12). Elevated NO expression has been fou...

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Section: Discussionsupporting

confidence: 89%

Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide

2007

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“…In contrast, the fever-enhancing effect of L-NAME at a neutral T a probably reflects enhanced vasoconstriction in the tail because L-NAME augmented the LPS-induced decreases in the HLI. These results are in agreement with a recent report (Kamerman et al, 2003) showing that the thermal effect of peripheral L-NAME in afebrile rats also depends on T a : L-NAME inhibits thermogenesis and causes hypothermia at a subneutral, but not at a neutral T a .…”

Section: Aa Steiner Et Alsupporting

confidence: 93%

Febrigenic signaling to the brain does not involve nitric oxide

Steiner

Rudaya

Ivanov

et al. 2004

British J Pharmacology

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1 The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear. It is also unclear whether NOS inhibitors attenuate fever by blocking febrigenic signaling or, alternatively, by suppressing thermogenesis in brown fat. 2 Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures (T c and T sk ) were monitored. 3 Study 1 was designed to determine whether the relatively stable, physiologically relevant forms of NO, that is, S-nitrosoalbumin (SNA) and S-nitrosoglutathione (SNG), are pyrogenic and whether they enhance LPS fever. At a neutral ambient temperature (T a ) of 311C, afebrile or LPS (1 mg kg À1 , i.v.)-treated rats were infused i.v. with SNA (0.34 or 4.1 mmol kg À1; the controls received NaNO 2 and albumin) or SNG (10 or 60 mmol kg À1 ; the controls received glutathione). T c of SNA-or SNG-treated rats never exceeded that of the controls. 4In Study 2, we tested whether the known fever-attenuating effect of the NOS inhibitor N o -nitro-Larginine methyl ester (L-NAME) at a subneutral T a (when fever is brought about by thermogenesis) also occurs at a neutral T a (when fever is brought about by skin vasoconstriction). At a subneutral T a of 241C, L-NAME (2.5 mg kg À1, i.v.) attenuated LPS (10 mg kg À1, i.v.) fever, presumably by inhibiting thermogenesis. At 311C, L-NAME enhanced LPS fever by augmenting skin vasoconstriction (T sk fall). 5 In summary, both SNA and SNG had no pyrogenic effect of their own and failed to enhance LPS fever; peripheral L-NAME attenuated only fever brought about by increased thermogenesis. It is concluded that NO is uninvolved in febrigenic signaling to the brain.

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“…Inhibitors of NOS suppress febrile responses to lipopolysaccharide (13,45) and interleukin 1 (34,44) (but see also Refs. 1 and 20) and inhibit stress-induced hyperthermia (11) and cold-induced thermogenesis (23). In the present study, a peripheral injection of 50 mg/kg L-NAME at dark onset elicited a 0.2-0.3°C drop in T br .…”

Section: Discussionsupporting

confidence: 51%

Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats

Ribeiro¹,

Kapás²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Ribeiro, Ana C., and Levente Kapás. Day-and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats. Am J Physiol Regul Integr Comp Physiol 289: R521-R531, 2005. First published April 28, 2005; doi:10.1152/ajpregu.00605.2004.-Previous studies suggest that nitric oxide (NO) may play a role in sleep regulation, particularly in the homeostatic process. The present studies were undertaken to compare the sleep effects of injecting a NO synthase (NOS) inhibitor when homeostatic sleep pressure is naturally highest (light onset) or when it is at its nadir (dark onset) in rats. Sleep, electroencephalogram delta-wave activity during nonrapid eye movement sleep (NREMS), also known as slow-wave activity (SWA), and brain temperature responses to three doses of the NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME; 5, 50, and 100 mg/kg) injected intraperitoneally at light or dark onset were examined in rats (n ϭ 6 to 8). The effects of 5 mg/kg L-NAME were determined in both normal and vagotomized (VX) rats. Light onset administration of 50 mg/kg L-NAME decreased NREMS amounts and suppressed SWA and increased rapid eye movement sleep (REMS) amounts. At dark onset, L-NAME injection also dose dependently suppressed SWA; however, unlike light onset injections, both NREMS and REMS amounts were increased after all three doses. Sleep responses to 5 mg/kg L-NAME were not different in control and VX rats, suggesting that the sleep effects of L-NAME are not mediated through the activation of sensory vagal mechanisms. The present findings suggest that timing of the injection is a major determinant of the sleep responses observed after systemic L-NAME injection in rats. N-nitro-L-arginine methyl ester; slow-wave activity; homeostatic regulation; vagotomy; suprachiasmatic nucleus; thermoregulation; electroencephalogram power spectrum SLEEP REGULATION RELIES ON the interplay between the homeostatic and circadian processes (5). The homeostatic component manifests itself as an increasing sleep pressure due to prior waking periods, whereas the circadian component is an oscillating process that permits sleep to occur only during low sleep threshold periods. Normally, increased homeostatic pressure coincides with periods of decreased sleep threshold, thus allowing sleep to occur. In nocturnal animals, such as rats, this occurs at the beginning of the light period. A growing number of studies suggest that nitric oxide (NO)-ergic mechanisms play a role in sleep regulation, particularly in the homeostatic component.The two-process model of sleep regulation postulates that the homeostatic process relies on a neuronal mechanism, the activity of which increases during wakefulness and is dissipated during sleep (5). There is evidence that the activity of NO-generating mechanisms in the brain stem, thalamus, and cortex fits this pattern. For example, NO is released in an activity-dependent manner from neurons in brain stem areas involved in sleep regulation (29). In rats, cortical (6) and thalamic (49) NO ...

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Inhibitors of nitric oxide synthesis block cold-induced thermogenesis in rats

Cited by 11 publications

References 23 publications

Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide

Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide

Febrigenic signaling to the brain does not involve nitric oxide

Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats

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