Although previous interest in the regulation of cerebral blood flow (CBF), and in the coupling of flow and cerebral metabolic rate for oxygen (CMR,,), was mainly focused on such coupling factors as extracellular H+ and KC, recent results have established the influence of neurotransmitters and neuromodulators. For example, it has been demonstrated that the catecholamines noradrenaline, dopamine, and adrenaline, when gaining access to intracerebral receptors, induce increases in CMR,, and CBF (MacKenzie et al. 1976a and b , McCulloch & Harper 1977, Berntman et al. 1978, and that serotonin has the opposite effects (Harper & MacKenzie 1977). It now seems that also prostaglandins exert a significant influence on CBF. Thus, Pickard & MacKenzie (1973), working on phencyclidine-anesthetized baboons, found that indomethacin (10 mg.kg-l) reduced normal CBF by about 40 % and considerably curtailed the circulatory response to induced hypercapnia.In the present study we repeated the experiments of Pickard & MacKenzie (1973) in another species under different anesthetic circumstances, and extended them to include arterial hypoxia as well.Since the results give novel information on the blood flow-metabolism couple in the brain they are reported in preliminary form.The experiments were performed on fed male Wistar rats, weighing 32C-415 g. Anesthesia was induced with 3 % halothane and 70% N,O, and continued during operative preparations on 1 % halothane and 70% N,O. The animals were tracheostomized, immobilized with tubocuraiine chloride (1.5 mgkg-I, Lv.), and ventilated artifically by a Starling type respirator. Both femoral arteries were cannulated to allow continuous blood pressure recording and sampling of arterial blood. One femoral vein was cannulated for administration of drugs. The caudal portion of the superior sagittal sinus was exposed by means of a small burr hole to obtain cerebral venous blood. In one group uf animals (see below) the adrenal pknds werc :-moved.After the completion of operative procedures, halothane supply was discontinued and the animals were heparinized (30 I.U:kg-') and maintained on 30% O2 and 70% N,O (or N,, see below) for a 30 min steady state period, rectal temperature being maintained close to 37 "C.Control animals maintained on 70% N,O were compared to 3 series of animals: normocapnic-normoxic, hypercapnic, and hypoxic. In the first series, one group of N,O-anesthetized animals was maintained normocapnic (Paco, 3540 mmHg) and normoxic (Pa,,,>lOo mmHg) for 30 min, following the injection of indomethacin in a dose of 10 mgkg-' i.v., before CBF and CMRo, were measured. Since indomethacin markedly reduced CBF an interaction with N,O had to be excluded. Therefore, indomethacin was also given to animals in which the nitrous oxide supply was discontinued for 15 min. In this group, the adrenal glands were removed and, in order to minimize pain and discomfort, the animals were given local anaesthesia and protected from external stimuli. In the hypercapnic series, indomethacin (10 mgkg-' i.v.) was ...

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO2) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg.kg-1i.v.) reduced CBF to 50% of control without a measurable effect on CMRO2. During hypercapnia (PaCO2 70-80 mmHg) the increase in CBF was reduced by about 80% but CMRO2 remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg.kg-1 and maximal effects were obtained with 3-5 mg.kg-1. Following i.v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1-2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO2 tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.

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