Mechanisms of hypoxia-induced cerebrovascular dilation in the newborn pig.
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 the pial arteriolar dilation to hypoxia (5 min, arterial PO2 approximately 30 mmHg) from 57 +/- 9 to 19 +/- 5%. Light/dye injury abolished the pial arteriolar dilation to hypercapnia but did not affect dilation to sodium nitroprusside. The pial arteriolar dilation to hypoxia was not affected by tetrodotoxin, N(omega)-nitro-L-arginine, glibenclamide, iberiotoxin, charybdotoxin, tetraethylammonium, or 8-phenyltheophylline. Hypoxia caused increases in the cerebral cortical production of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate. 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 P-450 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 P-450 epoxygenase metabolites of arachidonic acid.
Leffler
C W
CW
Department of Physiology and Biophysics, The University of Tennessee, Memphis 38163, USA.
Smith
J S
JS
Edrington
J L
JL
Zuckerman
S L
SL
Parfenova
H
H
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation
D015117:5,8,11,14-Eicosatetraynoic Acid; D002245:Carbon Dioxide; D009599:Nitroprusside; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D009637:Masoprocol; D013806:Theophylline; C028322:8-phenyltheophylline; D007545:Isoproterenol; D010100:Oxygen