Activated oxygen and arachidonate effects on newborn cerebral arterioles.
We have observed that pial arteriolar dilation in response to hypercapnia and hypotension is abolished after cerebral ischemia in newborn pigs. We determined whether direct generation of activated oxygen on the brain surface (OX: xanthine oxidase, hypoxanthine, FeCl3, and FeSO4) or topical arachidonate altered pial arteriolar responsiveness in a manner similarly to cerebral ischemia. OX, which generated more brain surface superoxide than reperfusion after ischemia, dilated pial arterioles. This dilation was reversed within 10 min of the end of exposure. OX produced ultrastructural changes in pial vessel endothelium and appeared to cause intravascular aggregation of granulocytes. After OX, prostanoid-dependent pial arteriolar dilations in response to hypercapnia and hypotension were attenuated, whereas constrictor responses to norepinephrine and acetylcholine and dilator responses to prostaglandin E2 and isoproterenol were not affected. After OX, hypercapnia increased cortical periarachnoid cerebrospinal fluid prostanoids modestly, whereas acetylcholine produced the normal strong stimulation of prostanoid synthesis. Arachidonate (10(-4) M and 7 x 10(-4) M) also caused reversible pial arteriolar dilation but did not alter subsequent pial arteriolar responses. Therefore, although arachidonate did not mimic the effects of ischemia-reperfusion on pial arteriolar reactivity, OX produced alterations that are qualitatively similar, although quantitatively less, than those produced by ischemia.
Leffler
C W
CW
Department of Physiology and Biophysics, Pediatrics, University of Tennessee, Memphis 38163.
Busija
D W
DW
Armstead
W M
WM
Shanklin
D R
DR
Mirro
R
R
Thelin
O
O
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology; D010100:Oxygen / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply; D011453:Prostaglandins / Q000378:metabolism; D013552:Swine; D014664:Vasodilation
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D010100:Oxygen