THE INHIBITION OF NOREPINEPHRINE-STIMULATED LIPOLYSIS BY ACUTE HYPOXIA

¹ Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington

The effect of acute hypoxia upon norepinephrine-stimulated lipolysis was investigated in puppies. Twenty-two animals were given norepinephrine (0.4 µg/kg/min) for 120 minutes. After 45 minutes of norepinephrine infusion and ventilation with air, plasma glycerol rose to 348 ± 19% and free fatty acids to 305 ± 29% mean control (mean ± S.E.). In five puppies continued on air (arterial pO₂,>75 mm Hg) and seven puppies given 13% oxygen-87% nitrogen (arterial pO₂ , 36-57 mm Hg) for 45 minutes and returned to air, plasma glycerol and free fatty acid levels declined slowly, although they remained elevated throughout the norepinephrine infusion. In contrast, in five other animals ventilated with 8% oxygen-92% nitrogen (arterial pO₂, 19-31 mm Hg) for 45 minutes, plasma glycerol and free fatty acids fell precipitously to near prenorepinephrine levels. During norepinephrine administration to animals ventilated with 8% oxygen-92% nitrogen, a significant negative correlation was found between plasma lactate and free fatty acids and between plasma lactate and glycerol. In the five remaining animals, L-lactate infusion replaced the period of hypoxia, resulting in large falls in plasma glycerol and free fatty acids. These observations indicate that norepinephrine-stimulated lipolysis is markedly inhibited by severe hypoxia and suggest that reduced mobilization contributes to the loss of free fatty acids as a fuel source in the severely hypoxic puppy. Furthermore, they imply that anaerobic glycolysis needs to be considered as a factor in impaired lipolysis during severe hypoxia.