Eicosanoid synthesis elicited by norepinephrine in piglet parietal cortex.
We investigated effects of exogenous norepinephrine and isoproterenol on pial arterial diameter and cerebral eicosanoid synthesis in anesthetized newborn pigs. Norepinephrine in artificial cerebrospinal fluid (CSF) constricted pial arteries from 203 +/- 27 micron (X +/- S.E.M.) to 164 +/- 18 micron (20 +/- 2%) (n = 21 vessels from 16 animals) at 10(-4) M. In the same animals, norepinephrine caused the concentration in CSF of 6-keto-prostaglandin F1 alpha to increase from 768 +/- 91 to 1544 +/- 151 pg/ml, thromboxane B2 to increase from 188 +/- 37 to 269 +/- 38 pg/ml, and prostaglandin E2 to increase from 2067 +/- 448 to 6575 +/- 751 pg/ml. Topical application of prostaglandin E2 in CSF to the cortical surface demonstrated that concentrations as low as 10,000 pg/ml were able to dilate pial arteries substantially. Blockade of cyclo-oxygenase activity by indomethacin (5-10 mg/kg, i.v.) potentiated pial arterial constriction to norepinephrine. Topical isoproterenol dilated pial arteries, but isoproterenol did not affect levels of measured eicosanoids in CSF. We conclude that norepinephrine elicits release of prostanoids from the cortical surface, and that these substances limit cerebrovascular constriction to norepinephrine.
D000818:Animals; D000831:Animals, Newborn; D002536:Cerebral Arteries / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004537:Eicosanoic Acids / Q000134:cerebrospinal fluid*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D013552:Swine
D004537:Eicosanoic Acids; D011458:Prostaglandins E; D007545:Isoproterenol; D009638:Norepinephrine