Effect of topical adenosine deaminase treatment on the functional hyperemic and hypoxic responses of cerebrocortical microcirculation.
The purpose of this study was to investigate the possible importance of adenosine in cerebrocortical vasodilatation accompanying brain activation (epileptic seizures and direct electrical stimulation) and hypoxia (arterial hypoxia and cyanide poisoning of the brain cortex). In chloralose-anesthetized cats a circumscribed area of the brain cortex was treated with adenosine deaminase (Type III; Sigma), which potently deaminates adenosine to the nonvasoactive inosine. Cerebrocortical vascular volume and fluorescence of reduced nicotinamide adenine dinucleotide were measured in vivo by surface fluororeflectometry. The responses of small pial and intracortical vessels to brain activation and hypoxia were studied in brain cortices superfused with artificial (mock) CSF and 5 U/ml adenosine deaminase. It was found that superficially applied adenosine deaminase readily diffuses onto the brain cortex. Prolonged pretreatment of the brain cortices with 0.025 U/ml adenosine deaminase eliminated almost completely the vasodilative effect of 10(-7) mol/ml adenosine. The inhibitory effect of the enzyme on adenosine-induced cortical vasodilatation was specific, because 5 U/ml adenosine deaminase did not attenuate the vasodilative potency of 10(-8) mol/ml 2-chloroadenosine. Adenosine deaminase (5 U/ml) pretreatment of the brain cortices did not diminish the cerebrocortical vascular volume, which increased with arterial hypoxia, topical cyanide poisoning, and direct electrical stimulation. However, it slightly decreased the vasodilative effect of epileptic seizures. On the basis of these results, it seems very unlikely that adenosine is a critical factor in the control of cerebrovascular tone during arterial hypoxia and brain activation.
D000243:Adenosine Deaminase / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D002415:Cats; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology; D006940:Hyperemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D009243:NAD; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase