Different Pial Arteriolar Responses to Acetylcholine in the Newborn and Juvenile Pig

Abstract

Using the closed cranial window technique, the present study was designed to test the hypothesis that the pial arteriolar response to acetylcholine is age dependent. In newborn pigs (1–5 days old) pretreated with the phosphodiesterase inhibitor isobutyl methyl xanthine (IBMX), acetylcholine (10⁻⁵ M) produced pial arteriolar constriction with no change 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 arteriolar diameter by 17 ± 1% and increased CSF cGMP by 2.1 ± 0.3-fold. Similar vascular and biochemical changes for acetylcholine were observed in juvenile pigs pretreated with only IBMX. In the absence of IBMX, acetylcholine produced modest pial constriction in juvenile pigs. In the IBMX-pretreated juvenile pigs, l-nitroarginine (LNA; 10⁻⁶ M) decreased pial arteriolar diameter by 15 ± 2% and blocked acetylcholine-induced dilation and associated changes in CSF cGMP. A23187, a calcium ionophore, and sodium nitroprusside (SNP) elicited similar dilation and changes in CSF cGMP in both age groups. LNA blocked A23187 dilation, but SNP dilation was unchanged. l-Arginine (10⁻³ M) partially restored acetylcholine- and A23187-induced dilation to indomethacin- and LNA-pretreated juvenile pigs. These data show that acetylcholine produces dilation in the juvenile pig through the production of the putative endothelium-derived relaxing factor (EDRF) nitric oxide but does not do so in the newborn period. We speculate that contributions of EDRF to the acetylcholine-induced changes in pial arteriolar diameter develop with age.