Permissive role of prostanoids in acetylcholine-induced cerebral vasoconstriction

W. M. Armstead, R. Mirro, D. W. Busija, Charles Leffler

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Abstract

The present study was designed to test the hypothesis that prostanoids play a permissive role in acetylcholine-induced cerebral constriction. Pial arterioles of newborn pigs were observed using a closed cranial window. Pial anteriolar constriction induced by topical acetylcholine (10-5 M) was blocked by indomethacin (5 mg/kg i.v.), but was restored when acetylcholine was coadministered with topical prostaglandin (PG) F(2α) (1 ng/ml), U46619 (1 ng/ml) or PGH2 (100 ng/ml). The restored acetylcholine response was blocked by topical pirenzepine (10-3 M), a muscarinic-1 antagonist. Constriction and ability of all three prostanoids to restore acetylcholine-induced constriction was blocked by SQ 29,548 (10-4 M), a purported thromboxane A2/PGH2 receptor antagonist. Subthreshold concentrations of U46619 and PGF(2α) (0.1 ng/ml) restored acetylcholine-induced constriction, whereas threshold and subthreshold concentrations of PGE2, platelet-activating factor and norepinephrine had no effect. Therefore, activation of the thromboxane A2/PGH2 receptor appears to be necessary for acetylcholine-induced constriction to occur. Thus, prostanoids appear to play a permissive role in acetylcholine-induced pial arteriolar constriction in newborn pigs.

Original languageEnglish (US)
Pages (from-to)1012-1019
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume251
Issue number3
StatePublished - 1989

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Vasoconstriction
Acetylcholine
Prostaglandins
Constriction
Prostaglandin H2 Receptors Thromboxane A2
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Prostaglandins F
Swine
Prostaglandin H2
Pirenzepine
Muscarinic Antagonists
Platelet Activating Factor
Arterioles
Dinoprostone
Indomethacin
Norepinephrine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Permissive role of prostanoids in acetylcholine-induced cerebral vasoconstriction. / Armstead, W. M.; Mirro, R.; Busija, D. W.; Leffler, Charles.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 251, No. 3, 1989, p. 1012-1019.

Research output: Contribution to journalArticle

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