Age dependence of cerebrovascular response mechanisms in the domestic pig. Zuckerman, S. L., W. M. Armstead, P. Hsu, M. Shibata, and C. W. Leffler. The Laboratory for Research in Neonatal Physiology, Departments of Physiology and Biophysics and Pediatrics, University of Tennessee, Memphis, TN 38163, Division of Critical Care and Pulmonary Medicine, St. Jude Children's Research Hospital, Memphis, TN 38101
APStracts 2:0565H, 1995.
Hypercapnia-induced cerebral vasodilation in the newborn pig is a prostanoid-associated response. In some adult models, hypercapnic cerebral vasodilation is associated with the generation of nitric oxide. Acetylcholine produces a nitric oxide dependent cerebral vasodilation in many adult models, but topical acetylcholine is a prostanoid associated cerebral vasoconstrictor in the newborn pig. We hypothesized that mediators influencing cerebral response can be age -dependent. Juvenile domestic pigs were compared to newborn pigs, and pial arteriolar diameters were measured using a closed cranial window during hypercapnia and topical acetylcholine (Ach) (10-5 M). 4 different conditions were explored : control, topical N_-nitro-L -arginine (LNA) (10-3 M), indomethacin (5mg/kg i.v.), and both LNA and indomethacin. All animals were anesthetized with [alpha]-chloralose. As opposed to the complete block in the newborn, indomethacin only partially attenuated the hypercapnic cerebral vasodilation in the juvenile pig. LNA which had no effect on the response of the newborn produced a partial attenuation of the hypercapnic response of the juvenile. The combination of indomethacin and LNA blocked the response in both age groups. Topical Ach in both age groups initially produced cerebral vasoconstriction; but, in the juvenile, this was followed by a sustained cerebral vasodilation. Indomethacin blocked the early vasoconstriction in both age groups. LNA, which had no effect in the response of the newborn to Ach, blocked the vasodilation seen in the juvenile. The combination of both inhibitors blocked all response to Ach in the juvenile. These data indicate that while the cerebral vascular responses to Ach and hypercapnia are prostanoid associated and nitric oxide independent in the newborn pig, nitric oxide assumes an increasing role in dilatory responses with development.

Received 24 May 1995; accepted in final form 8 December 1995.
APS Manuscript Number H484-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95