Effects of Indomethacin on Cerebral Blood Flow and Oxygen Consumption in Barbiturate-Anesthetized Normocapnic and Hypercapnic Rats

Abstract

In spite of the fact that the problem has been studied over many decades, the factors that adjust the cerebral blood flow (CBF) to functional and metabolic demands have not yet been defined. Re cent results indicate that some of these missing coupling factors may be provided by products of the fatty acid cyclo-oxygenase, i. e. , by prostaglandins and related substances. The evidence comes from Abbreviations used: Cao2, oxygen content; A VD02, ar teriovenous oxygen difference. 109studies in which the cyclo-oxygenase was inhibited by indomethacin, a potent inhibitor of the enzyme in brain and other tissues (see Flower, 1974; Wolfe et aI. , 1976; Abdel-Halim et aI. , 1978). The original report describing an effect of in domethacin on CBF was published by Pickard and MacKenzie (1973), who administered the drug by intravenous (10 mg kg-I) or intracarotid (0.04-0.2 mg kg-I min-I) routes in phencyclidine-N20 anesthetized baboons, measuring CBF with a 133Xe clearance technique. The authors found that the drug reduced control CBF by an average of 38% and that it markedly attenuated the CBF response to

A Slow or Modulatory Role of Astrocytes in Neurovascular Coupling

“…Inhibition of CYP450 isozymes and therefore the production of EETs by miconazole or MS‐PPOH reduces basal cerebral blood flow by 20–30% . In a similar fashion, the non‐specific inhibition of COX‐1&2 pathways via indomethacin has been observed to significantly reduce resting cerebral blood flow . These studies indicate that brain‐derived vasodilators may be acting tonically to help set baseline blood flow.…”

Posterior hypothalamic activation in paroxysmal hemicrania

“…In humans, the reported decrease in global CBF ranges from 18 to 47% 31–40. This indomethacin‐induced reduction in CBF has been reported to be relatively uniform throughout the brain in animal studies41, 42 and appears to be limited to parenchymal vessels. Pial vessels and larger cerebral vessels are either unaffected or relaxed by indomethacin 43–46.…”

Sympathetic effects on cerebral and ocular blood flow in rabbits pretreated with indomethacin

“…A similar. relatively moderate effect was observed in rats under pentobarbital anesthesia (Dahlgren & Siesjo 1981).…”