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Effects of Phorbol Esters on Pial Arteriolar Diameter and Brain Production of Prostanoids in Piglets

We determined the effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C, on pial arteriolar diameter and cerebrospinal fluid (CSF) prostanoid levels in newborn pigs. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital micro...

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Bibliographic Details
Published in:Circulation research 1991-11, Vol.69 (5), p.1253-1258
Main Authors: Busija, David W, Leffler, Charles W
Format: Article
Language:English
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Summary:We determined the effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C, on pial arteriolar diameter and cerebrospinal fluid (CSF) prostanoid levels in newborn pigs. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. In addition, CSF was sampled from under the window, and prostanoid levels (prostaglandin [PG] E2, 6-keto-PGF1∞, PGF2∞, and thromboxane B2) were determined by radioimmunoassay. Diameter and CSF prostanoid levels were determined during application of artificial CSF containing no drugs and during application of 10, 10, and 10 M PDB. We also determined effects of 4α-phorbol 12,13-didecanoate (4α-PDD), a phorbol ester that does not activate protein kinase C, and dimethyl sulfoxide, the vehicle for the phorbol esters, on pial arteriolar diameter and CSF prostanoid levels. Initial diameters were 100–200 μm. At 10-10 M, PDB progressively constricted pial arterioles and increased CSF levels of prostanoids; the other phorbol ester and dimethyl sulfoxide had no such effects. Baseline arteriolar diameter was 147±17,um (mean±SEM), and diameter was 140±17 μm at 10 M PDB, 120±18 μm at 10 M PDB (p
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.69.5.1253