Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 437-442

Role of Nitric Oxide in Thermoregulation and Hypoxic Ventilatory Response in Obese Zucker Rats

HITOSHI NAKANO, SHIN-DA LEE, ANDREW D. RAY, JOHN A. KRASNEY, and GASPAR A. FARKAS

Department of Physiology and Biophysics, Department of Physical Therapy, Exercise and Nutrition Sciences, and Center for Sleep Disorders Research, University at Buffalo, The State University of New York, Buffalo, New York

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 underwent a sustained hypoxic challenge. Body temperature (Tb), oxygen consumption ( O₂) and ventilation ( E) were measured during room air and during 30-min of hypoxia (10% O₂) 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 inhibitor, or equal volume of vehicle (dimethyl sulfoxide: DMSO) as control. Tb in obese rats during room air was significantly lower than that of lean rats. Hypoxia induced a more pronounced drop in Tb and O₂ in lean rats than in obese rats. Tb in lean Z rats dropped significantly by ~ 0.2° C after L-NAME and, more markedly, by ~ 1.1° C 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 hypometabolism in lean rats, but not in obese rats. Lean rats exhibited an abrupt increase in E in response to hypoxia followed by a gradual decline in E. In contrast, obese rats displayed an initial increase in E that plateaued during sustained hypoxia. Both L-NAME and 7-NI induced marked decreases in E during room air and hypoxia compared with control lean rats, whereas E was virtually unaffected by either agent in obese rats. The present results suggest that the blunted thermoregulatory and ventilatory responses to hypoxia in obese Z rats may be attributed to reduced activity of NOS in the central nervous system.

Keywords: obesity; control of breathing; metabolism; nitric oxide synthase

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