MECHANISMS OF HYPOXIA-INDUCED CEREBROVASCULAR DILATION IN THE NEWBORNPIG

The hypothesis that endothelium dependent components contribute to the cerebromicrovascular dilation to hypoxia in the newborn pig was addre ssed. Piglets anesthetized with ketamine-acepromazine and maintained o n alpha-chloralose were equipped with closed cranial windows. Injury t o the endothelium of pial arterioles was produced by light activation of fluorescein dye. Light/dye injury reduced the pial arteriolar dilat ion to hypoxia (5 min, arterial PO2 congruent to 30 mmHg) from 57 +/- 9 to 19 +/- 5%. Light/dye injury abolished the pial arteriolar dilatio n to hypercapnia but did not affect dilation to sodium nitroprusside. The pial arteriolar dilation to hypoxia was not affected by tetrodotox in, N-omega-nitro-L-arginine, glibenclamide, iberiotoxin, charybdotoxi n, tetraethylammonium, or 8-phenyltheophylline. Hypoxia caused increas es in the cerebral cortical production of adenosine 3',5'-cyclic monop hosphate and guanosine 3',5'-cyclic monophosphate. Cerebral vasodilati on 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 P-450 epoxygenase inhibitor miconazol decrea sed cerebral vasodilation to hypoxia from 45 +/- 5 to 17 +/- 4%. There fore, the vascular endothelium appears to participate in cerebral micr ovascular dilation to hypoxia in newborn pigs. The mechanism may inclu de cytochrome P-450 epoxygenase metabolites of arachidonic acid.