Permissive role of prostanoids in acetylcholine-induced cerebral vasoconstriction.
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 arteriolar 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) F2 alpha (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 PGF2 alpha (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.
Armstead
W M
WM
Department of Physiology and Biophysics, University of Tennessee, Memphis.
Mirro
R
R
Busija
D W
DW
Leffler
C W
CW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D044262:Prostaglandin H2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D000109:Acetylcholine