HYPERCAPNIA-INDUCED INCREASES IN CEREBRAL BLOOD-FLOW - ROLES OF ADENOSINE, NITRIC-OXIDE AND CORTICAL AROUSAL

The roles of nitric oxide, adenosine and cortical arousal in the respo nse to 7.5% CO2 inhalation were investigated by measuring cerebral blo od flow bilaterally in the rat somatosensory cortices with laser-Doppl er flow probes. Administration of N-omega-nitro-L-arginine methyl este r (L-NAME; 20 mg/kg, i.v.) significantly attenuated the response to hy percapnia (mean decrease of 47%). This effect was partially reversed b y a subsequent administration of L-arginine. Caffeine (10 mg/kg, i.v.) also significantly reduced hypercapnic responses (mean decrease of 44 %). Caffeine administration was also associated with a tendency for an imals to exhibit electrocorticographic signs of arousal; often associa ted with a reduction in the attenuation of the flow response to CO2 in halation. 8-(3-Chlorostyryl) caffeine (CSC, 1.0 mg/kg), a selective an tagonist at adenosine A(2a) striatal receptors failed to attenuate CO2 -evoked responses, whereas CGS 15943, a less selective A(2a) receptor antagonist, significantly reduced CO2 responses. These data from the r at suggest (1) that both nitric oxide and adenosine may contribute to pial arteriolar vasodilatation during hypercapnia, and (2) that CO2 in halation acts as a potent stimulus for cortical arousal, with enhanced neuronal activity contributing to the vascular response. The effects of administration of adenosine antagonists, such as the methylxanthine s antagonists caffeine and theophylline, on CBF responses to hypercapn ia can potentially be negated by the ability of these agents to facili tate CO2-induced cortical arousal.