AGE-DEPENDENCE OF CEREBROVASCULAR RESPONSE MECHANISMS IN DOMESTIC PIGS

Hypercapnia-induced cerebral vasodilation in the newborn pig is a pros tanoid-associated response. In some adult models, hypercapnic cerebral vasodilation is associated with the generation of nitric oxide (NO). Acetylcholine (ACh) produces a NO-dependent cerebral vasodilation in m any adult models, but topical ACh is a prostanoid-associated cerebral vasoconstrictor in the newborn pig. We hypothesized that mediators inf luencing cerebral response can be age dependent. Juvenile domestic pig s were compared with newborn pigs, and pial arteriolar diameters were measured by use of a closed cranial window during hypercapnia and topi cal ACh (10(-5) M). Four different conditions were explored: control, topical N-omega-nitro-L-arginine (L-NNA, 10(-3) M), indomethacin (5 mg /kg iv), and both L-NNA and indomethacin. All animals were anesthetize d with alpha-chloralose. As opposed to the complete block in the newbo rn, indomethacin only partially attenuated the hypercapnic cerebral va sodilation in the juvenile pig. L-NNA, which had no effect on the resp onse of the newborn, produced a partial attenuation of the hypercapnic response of the juvenile. The combination of indomethacin and L-NNA b locked the response in both age groups. Topical ACh in both age groups initially produced cerebral vasoconstriction, but, in the juvenile, t his was followed by a sustained cerebral vasodilation. Indomethacin bl ocked the early vasoconstriction in both age groups. L-NNA, which had no effect in the response of the newborn to ACh, blocked the vasodilat ion seen in the juvenile. The combination of both inhibitors blocked a ll response to ACh in the juvenile. These data indicate that although the cerebral vascular responses to ACh and hypercapnia are prostanoid associated and NO independent in the newborn pig, NO assumes an increa sing role in dilatory responses with development.