An earlier study has demonstrated that indomethacin, a prostaglandin synthesis inhibitor, blocks the cerebrovascular response to hypercapnia. This response is believed to be mediated by a lowering of pH in the cerebral interstitial fluid. Should autoregulation of cerebral blood flow (CBF) to changing perfusion pressure also be mediated by a changing interstitial pH (the "metabolic" theory), then indomethacin should impair autoregulation. This hypothesis was tested in anesthetized baboons. CBF was measured by the intracarotid 133Xe clearance technique; the preparation and the indomethacin protocol were identical to those of our previous investigation. Arterial pressure was increased by the intravenous infusion of angiotensin and decreased by controlled hemorrhage. Indomethacin was given by continuous infusion into the internal carotid artery. Although it reduced resting CBF, the cerebrovascular response to changing perfusion pressure was unchanged. Because indomethacin affects the response to changing CO2 but not that to changing perfusion pressure, the mechanisms for these two reactions presumably are different and it is improbable that changing interstitial pH is responsible for autoregulation in the cerebral circulation.

1Noradrenaline infused into the internal carotid artery of the dog (0.01-1 Mg kg-' min-)constricts the blood vessels of the cortex. This constriction is mediated by the action of noradrenaline on a-adrenoceptors of the cerebral arteries.2 Intravenous (1 ,g kg-' min-) or intra common carotid arterial (0.01-1 Mg kg-' min-) infusions of noradrenaline cause an increase in cortical blood flow that can be dissociated from changes in blood pressure. 3 The effect of intravenous noradrenaline on the cortical blood vessels and metabolism is blocked by high Paco2 levels, or by the prior administration of (+)-propranolol. (+)-Propranolol is without such effect. 4 Following section of both vagi and both sinus nerves, intravenous noradrenaline fails to cause an increase in cortical blood flow. 5 In another series of animals the area of the carotid bifurcation was vascularly isolated and perfused with blood from a second dog. Chemoreceptor and baroreceptor activity was shown to be intact. 6 Administration of 5% CO2 to the donor dog caused an increase in cerebral blood flow in the recipient dog. 9 This evidence suggests that the cerebrovasodilatation observed following intravenous noradrenaline is reflex and is triggered by chemoreceptor activity. 10 The evidence also suggests that the antagonism of the cortical dilatory effects of intravenous noradrenaline by raised Paco2 in the intact animal must be at a site different from the peripheral chemoreceptors.

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