Role of Hypoxia and Acetylcholine in the Regulation of Cerebral Blood Flow

Abstract

It is well-known that the cerebral cortex is heterogeneously supplied with oxygen. According to microelectrode measurements, PO₂ at some microregions of the brain cortex is close to zero mmHg (Silver, 1966; Metzger and Heuber, 1977). Supporting these data, Rosenthal et al. (1976) showed that the oxido-reduction state of cytochrome a,a₃ in the brain cortex is shifted toward a more oxidized state if cerebral oxygen supply is increased. On the basis of this finding, Rosenthal et al. (1976), in accordance with Davies and Bronk (1957), suggested that under physiological conditions the brain cortex is on the border of slight hypoxia. This assumption seemed to be supported by the data of Kontos et al. (1978) and Morii, Winn and Berne, (1983). They showed that the autoregulatory dilatation of pial arteries can be counteracted by superfusion of the brain cortex with oxygen-saturated mock cerebrospinal fluid (CSF) or fluorocarbon (Kontos et al., 1978), and the resting cerebral blood flow (CBF) can be decreased by systemic theophylline treatment (Morii et al., 1983). However, other investigators (Leniger-Follert, 1985; Rubin and Bohlen, 1985) found no change in cortical PO₂ during autoregulation, and resting CBF was not altered by systemic theophylline treatment in Emerson and Raymond’s (1981) experiments. This controversy in the literature led us to investigate the effects of an excess of oxygen on the steady NAD/NADH redox state and autoregulation of the brain cortex. In addition, we studied the effect of topical adenosine deaminase and theophylline treatment of the brain cortex in order to see whether adenosine (ADO) contributes to the maintenance of resting CBF.