Mechanisms of hypoxia-induced cerebrovascular dilation in the
newborn pig.
Leffler, Charles W., J. Suzanne Smith, Jamie L. Edrington, Samuel L.
Zuckerman, and Helena Parfenova.
Laboratory for Research in Neonatal Physiology, Department of
Physiology and Biophysics, The University of Tennessee, Memphis, 894
Union Avenue, Memphis, TN 38163
APStracts 3:0454H, 1996.
The hypothesis that endothelium-dependent components contribute to the
cerebromicrovascular dilation to hypoxia in the newborn pig was
addressed. Piglets anesthetized with ketamine/acepromazine and
maintained on [alpha]-chloralose were equipped with closed cranial
windows. Injury to the endothelium of pial arterioles was produced by
light activation of fluorescein dye. Light/dye injury reduced pial
arteriolar dilation to hypoxia (5 min, PaO2 _ 30 mmHg) from 57 +/- 9%
to 19 +/- 5%. Light/dye injury abolished pial arteriolar dilation to
hypercapnia but did not affect dilation to sodium nitroprusside. Pial
arteriolar dilation to hypoxia was not affected by tetrodotoxin, Nw
-nitro-L-arginine, glibenclamide, iberiotoxin, charybdotoxin,
tetraethylammonium, or 8-phenyltheophylline. Hypoxia caused increases
in cerebral cortical production of cAMP and cGMP. Cerebral
vasodilation to hypoxia was inhibited by 5, 8, 11, 14
eicosatetraynoic acid, but was not greatly affected by cyclooxygenase
or lipoxygenase inhibitors. In contrast, the cytochrome P450
epoxygenase inhibitor, miconazol, decreased cerebral vasodilation to
hypoxia from 45 +/- 5% to 17 +/- 4%. Therefore, the vascular
endothelium appears to participate in cerebral microvascular dilation
to hypoxia in newborn pigs. The mechanism may include cytochrome P450
epoxygenase metabolites of arachidonic acid.
Received 10 July 1996; accepted in final form 27 September 1996.
APS Manuscript Number H614-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996