Histamine dilates pial arterioles of newborn pigs through prostanoid production.
To test the hypothesis that histamine would dilate pial arterioles via a prostanoid mechanism, histamine was placed on the brain surface of anesthetized newborn pigs via a closed cranial window. Pial arteriolar diameters were measured after topical application of 10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) M histamine. In addition, cortical cerebrospinal fluid (CSF) was collected for radioimmunoassay of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and prostaglandin F2 alpha (PGF2 alpha). The animals were then randomized to receive either indomethacin trihydrate (5 mg/kg, iv) or an equal volume of saline (vehicle). The protocol then was repeated. Histamine (before indomethacin or vehicle infusion) caused concentration-dependent vasodilation. This vasodilation was accompanied by a significant increase in cortical CSF 6-keto-PGF1 alpha and PGE2. Concentrations of TxB2, PGD2, and PGF2 alpha were not altered significantly by histamine application. Pretreatment with indomethacin blocked the histamine-induced cerebral vasodilation, but vasodilation after vehicle was intact. These data imply that histamine dilates the pial arterioles of newborn pigs by stimulating the synthesis of vasodilator prostanoids.
Mirro
R
R
Department of Pediatrics, University of Tennessee, Memphis 38163.
Busija
D W
DW
Armstead
W M
WM
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D011453:Prostaglandins / Q000096:biosynthesis*; D012016:Reference Values; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D011453:Prostaglandins; D006632:Histamine; D007213:Indomethacin