EFFECTS OF INDOMETHACIN ON CEREBRAL VASODILATOR RESPONSES TO ARACHIDONIC-ACID AND HYPERCAPNIA IN NEWBORN PIGS
EFFECTS OF INDOMETHACIN ON CEREBRAL VASODILATOR RESPONSES TO ARACHIDONIC-ACID AND HYPERCAPNIA IN NEWBORN PIGS
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DOI：
10.1203/00006450-199306000-00016
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发表时间：
1993-06-01
影响因子：
3.6
通讯作者：
ZUCKERMAN, S
中科院分区：
文献类型：
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作者：
LEFFLER, CW;MIRRO, R;ZUCKERMAN, S
在封闭颅窗、氯氯糖麻醉的新生猪中，研究了局部应用花生四烯酸、外源性花生四烯酸向前列腺素的转化、以及在吲哚美辛（5mg /kg静脉注射）治疗前和治疗后的进展时间内，动脉小动脉对高碳酸血症的反应。在使用吲哚美辛、花生四烯酸和高碳酸血症治疗前，动脉小动脉扩张，蛛网膜周围脑脊液6-酮-前列腺素（PG） f1 α和PGE2浓度升高。吲哚美辛治疗1 h后，扩张和前列腺素合成被阻断。在吲哚美辛治疗后2小时，高碳酸血症导致动脉小动脉明显扩张，在3小时后，两种刺激的扩张都恢复到吲哚美辛治疗前的水平。窗下脑脊液中6-酮- pgf1 α和PGE2升高监测到外源性花生四烯酸向前列腺素转化的抑制作用也在使用吲哚美辛治疗后3小时逆转。反复的吲哚美辛治疗再次阻断了脑表面花生四烯酸向前列腺素的扩张和转化。当系统给药时，吲哚美辛对血管的有效性持续时间短的可能性需要考虑，无论是当它被用作了解PGH合成酶产物对控制脑循环的贡献的探针，还是当它被用于治疗试图改变新生儿脑循环时。
Responses of pial arterioles to topically applied arachidonic acid, conversion of exogenous arachidonic acid to prostanoids, and pial arteriolar dilation to hypercapnia were examined before and at progressive times after treatment with indomethacin (5 mg/kg i.v.) in chloralose-anesthetized newborn pigs with closed cranial windows. Before treatment with indomethacin, arachidonic acid and hypercapnia dilated pial arterioles and increased cortical periarachnoid cerebrospinal fluid concentrations of 6-keto-prostaglandin (PG) F1alpha and PGE2. One h after indomethacin treatment, the dilations and prostanoid synthesis were blocked. By 2 h after indomethacin treatment, hypercapnia produced significant dilation of pial arterioles, and dilation to both stimuli had returned to preindomethacin levels by 3 h. Inhibition of conversion of exogenous arachidonic acid to prostanoids as monitored by increases in 6-keto-PGF1alpha and PGE2 in cerebrospinal fluid under the window also was reversed by 3 h after treatment with indomethacin. Repeated indomethacin treatment again blocked dilations and conversion of arachidonic acid to prostanoids on the brain surface. The possibility of short duration of vascular effectiveness of indomethacin when it is administered systemically needs to be considered, both when it is used as a probe for understanding contributions of PGH synthase products to control of cerebral circulation and when it is used therapeutically in attempts to alter the newborn cerebral circulation.