Brain metabolism in uremic and adenosine-infused rats

Abstract

A B S T R A C T Analyses of nucleotides and glycolytic intermediates were performed on perchlorate extracts of blood and quick-frozen brain from rats nephrectomized 48 hr previously, and from rats infused for 6 hr with adenosine or AMP. Blood nucleotides of acutely uremic rats were normal. Uremic brain showed an increase of creatine phosphate (CP), ATP, and glucose with a corresponding decrease in creatine, ADP, AMP, and lactate. Other nucleotide triphosphates were increased, but total adenine nucleotide in brain was unchanged. Uremic brain failed to use ATP or produce ADP, AMP, and lactate at normal rates when subjected to the stress of ischemic anoxia. Although levels of cation responsive ATPase in extracts of uremic brain were normal, the inhibition of glycolysis in the intact brain appeared to be due to a failure of ATP hydrolysis (a diminished ATPase activity). Adenosine infusion produced mild azotemia, marked hyperglycemia, an increase in blood ATP,-and an increase in total blood adenine nucleotide. Brain from rats infused with adenosine or AMP also had high levels of ATP, creatine phosphate, and glucose, whereas levels of ADP, AMP, and lactate were low. However these brains responded with normal use of ATP and normal production of lactate when stimulated by ischemic anoxia.

Uremic Encephalopathy

“…Thus, the uremic brain in experimental uremia appears to use less adenosine triphosphate and to produce less aadenosine diphosphate, adenosine monoposphate and lactate. These changes are associated with a decrease in both brain metabolic rate and cerebral oxygen consumption (Mahoney et al, 1984;Van den Noort et al, 1968) and are consistent with a generalized decrease in brain energy use. Moreover, an inhibition of cerebral sodium-potassium-ATPase was shown in experimental uremic animals (Burn & Bates, 1998;Minkoff et al, 1972).…”