Abstract
The effects of two prostaglandin synthesis inhibitors on brain oxidative metabolism and cerebral blood volume were studied by the nicotinamide adenine dinucleotide (reduced) (NADH) fluorescence technique in rats, Indomethacin (5, 10, and 15 mg/kg) and sodium salicylate (50, 100, and 300 mg/kg) were administered intravenously to groups of rats anesthetized with either nitrous oxide or pentobarbital (40 mg/kg, i.p.). The effects of pentobarbital alone were also examined: pentobarbital induced a progressive reduction in blood volume 4 min following intraperitoneal administration. A reduced NADH fluorescence (oxidation) was noted approximately 9 min after pentobarbital treatment. In N2O-anesthetized rats, the effects of salicylate were dose-dependent. Low doses (50 and 100 mg/kg) decreased both blood volume and NADH fluorescence; in contrast, salicylate at 300 mg/kg increased blood volume and NADH fluorescence. Following pentobarbital, the effects of salicylate (50 and 100 mg/kg) were reversed: increases in both blood volume and NADH fluorescence were seen. In the absence of pentobarbital, it would appear that salicylate induces a cerebral vasoconstriction, an effect that may be obscured by a central stimulation provoked by this drug. Under N2O anesthesia, indomethacin, in a dose-related manner, induced a decrease in blood volume that was accompanied by a dose-related increase in NADH fluorescence (reduction). The changes induced by the highest dose of indomethacin (15 mg/kg) were essentially abolished by pentobarbital. These results support those studies in which indomethacin-induced cerebral vasoconstriction could be abolished by barbiturates. Furthermore, our experiments demonstrate, following indomethacin infusion, a decrease in brain oxidative metabolism. With indomethacin, the NADH fluorescence technique would suggest that the metabolic effects of this drug are essentially to reduce oxygen consumption without any noticeable effect on glucose utilization; the observed changes in cerebral perfusion are likely to be directly correlated with the decreases in cerebral oxygen consumption.