Prostanoid synthesis and vascular responses to exogenous arachidonic acid following cerebral ischemia in piglets.
In newborn pigs, cerebral ischemia abolishes both increased cerebral prostanoid production and cerebral vasodilation in response to hypercapnia and hypotension. Attenuation of prostaglandin endoperoxide synthase activity could account for the failure to increase prostanoid synthesis and loss of responses to these stimuli. To test this possibility, arachidonic acid (3, 6, or 30 micrograms/ml) was placed under cranial windows in newborn pigs that had been exposed to 20 min of cerebral ischemia. The conversion to prostanoids and pial arteriolar responses to the arachidonic acid were measured. At all three concentrations, arachidonic acid caused similar increases in pial arteriolar diameter in sham control piglets and piglets 1 hr postischemia. Topical arachidonic acid caused dose-dependent increases of PGE2 in cortical periarachnoid cerebral spinal fluid. 6-keto-PGF1 alpha and TXB2 only increased at the highest concentration of arachidonic acid (30 micrograms/ml). Cerebral ischemia did not decrease the conversion of any concentration of arachidonic acid to PGE2, 6-keto-PGF1 alpha, or TXB2. We conclude that ischemia and subsequent reperfusion do not result in inhibition of prostaglandin endoperoxide synthase in the newborn pig brain. Therefore, the mechanism for the impaired prostanoid production in response to hypercapnia and hypotension following cerebral ischemia appears to involve reduction in release of free arachidonic acid.
Leffler
C W
CW
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Armstead
W M
WM
Busija
D W
DW
Thelin
O
O
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis*; D019736:Prostheses and Implants; D013552:Swine
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid