Summary:The effect of local administration of vasodila tive concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size dependent dilations of pial arterioles [small = 41 ± 7 !-Lm (mean ± SD), intermediate = 78 ± 13 !-Lm, and large = 176 ± 57 !-Lm in diameter 1 occurred in response to graded hypercapnia alone (P aco2 = 58 and 98 mm Hg) and to superfusions of 2-CADO 00-5 M) during normocapnia; the magnitude of the dilative response to each of these The mechanism underlying hypercapnic hyper emia in brain is not well understood. A hypercap nia-induced increase in extracellular hydrogen ion concentration is likely to be the initial step of this process (Kontos et aI., 1977), but hydrogen ion may not be the final effector. There is evidence that the hyperemia in newborn animals results from hydro gen ion-stimulated production of vasodilative pros tanoids (Wagerle and Mishra, 1988; Leffler et aI., 1989). The purine metabolite adenosine has also been hypothesized to participate in the mediation of hypercapnic vasodilation, based on studies in which adenosine receptor blockade reduced hypercapnia- Abbreviations used: ANOYA, analysis of variance; 2-CADO, 2-chloroadenosine.
656stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10-5 M 2-CADO, which doubled CBF during normo capnia, did not affect the hyperemic response of the pa renchymal circulation to graded hypercapnia (P aco2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not in volved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions in duced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.