Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats

To examine the role of nitric oxide (NO) on thermoregulation and control of breathing in obesity, awake obese and age-matched lean Zucker (Z) rats und erwent a sustained hypoxic challenge. Body temperature (Tb), oxygen consump tion (Vo(2)) and ventilation (VE) were measured during room air and during 30-min of hypoxia (10% O-2) after intraperitoneal administration of either 100 mg/kg of N-G-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor, 25 mg/kg of 7-nitroindazole (7-NI), a selective neuronal NOS inh ibitor, or equal volume of vehicle (dimethyl sulfoxide: DMSO) as control. T b in obese rats during room air was significantly lower than that of lean r ats. Hypoxia induced a more pronounced drop in Tb and Vo(2) in lean rats th an in obese! rats. Tb in lean Z rats dropped significantly by similar to0.2 degreesC after L-NAME and, more markedly, by similar to1.1 degreesC after 7-NI compared with control during room air, whereas Tb in obese Z rats was unaffected. L-NAME and 7-NI attenuated hypoxia-induced hypothermia or hypom etabolism in lean rats, but not in obese rats. Lean rats exhibited an abrup t increase in VE in response to hypoxia followed by a gradual decline in VE . In contrast, obese rats displayed an initial increase in VE that plateaue d during sustained hypoxia. Both L-NAME and 7-NI induced marked decreases i n VE during room air and hypoxia compared with control lean rats, whereas V E was virtually unaffected by either agent in obese rats. The present resul ts suggest that the blunted thermoregulatory and ventilatory responses to h ypoxia in obese Z rats may be attributed to reduced activity of NOS in the central nervous system.