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 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.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|