Armstead W M, Mirro R, Busija D W, Leffler C W
Department of Physiology and Biophysics, University of Tennessee, Memphis.
J Pharmacol Exp Ther. 1989 Dec;251(3):1012-9.
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.
本研究旨在验证前列腺素在乙酰胆碱诱导的脑动脉收缩中起允许作用这一假说。使用封闭的颅窗观察新生猪的软脑膜小动脉。局部应用乙酰胆碱（10⁻⁵ M）诱导的软脑膜小动脉收缩被吲哚美辛（5 mg/kg静脉注射）阻断，但当乙酰胆碱与局部前列腺素（PG）F2α（1 ng/ml）、U46619（1 ng/ml）或PGH2（100 ng/ml）共同给药时，收缩得以恢复。恢复后的乙酰胆碱反应被毒蕈碱-1拮抗剂哌仑西平（10⁻³ M）局部应用所阻断。三种前列腺素恢复乙酰胆碱诱导的收缩的作用及收缩均被SQ 29548（10⁻⁴ M）阻断，SQ 29548是一种所谓的血栓素A2/PGH2受体拮抗剂。亚阈值浓度的U46619和PGF2α（0.1 ng/ml）恢复了乙酰胆碱诱导的收缩，而阈值和亚阈值浓度的PGE2、血小板活化因子和去甲肾上腺素则无作用。因此，血栓素A2/PGH2受体的激活似乎是乙酰胆碱诱导收缩发生所必需的。所以，前列腺素在新生猪乙酰胆碱诱导的软脑膜小动脉收缩中似乎起允许作用。
