DIFFERENT PIAL ARTERIOLAR RESPONSES TO ACETYLCHOLINE IN THE NEWBORN AND JUVENILE PIG

Using the closed cranial window technique, the present study was desig ned to test the hypothesis that the pial arteriolar response to acetyl choline is age dependent. In newborn pigs (1-5 days old) pretreated wi th the phosphodiesterase inhibitor isobutyl methyl xanthine (IBMX), ac etylcholine (10(-5) M) produced pial arteriolar constriction with no c hange in CSF cyclic GMP (cGMP) that was blocked by indomethacin (5 mg/ kg i.v.). In contrast, in indomethacin- and IBMX-treated juvenile pigs (3-4 weeks old), acetylcholine (10(-) M) increased the pial arteriola r diameter by 17 +/- 1% and increased CSF cGMP by 2.1 +/- 0.3-fold. Si milar vascular and biochemical changes for acetylcholine were observed in juvenile pigs pretreated with only IBMX. In the absence of IBMX, a cetylcholine produced modest pial constriction in juvenile pigs. In th e IBMX-pretreated juvenile pigs, L-nitroarginine (LNA; 10(-6) M) decre ased pial arteriolar diameter by 15 +/- 2% and blocked acetylcholine-i nduced dilation and associated changes in CSF cGMP. A23187, a calcium ionophore, and sodium nitroprusside (SNP) elicited similar dilation an d changes in CSF cGMP in both age groups. LNA blocked A23187 dilation, but SNP dilation was unchanged. L-Arginine (10(-3) M) partially resto red acetylcholine- and A23187-induced dilation to indomethacin- and LN A-pretreated juvenile pigs. These data show that acetylcholine produce s dilation in the juvenile pig through the production of the putative endothelium-derived relaxing factor (EDRF) nitric oxide but does not d o so in the newborn period. We speculate that contributions of EDRF to the acetylcholine-induced changes in pial arteriolar diameter develop with age.