Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries

Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries
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内皮血栓素 A2 在犬脑动脉对乙酰胆碱和花生四烯酸的静息张力和收缩反应中的可能作用

DOI:
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发表时间:
1987
影响因子:
3
通讯作者:
K. Fukui
K. Fukui
中科院分区:
医学4区
文献类型:
--
作者:
H. Shirahase;H. Usui;K. Kurahashi;M. Fujiwara;K. Fukui

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本文用放射免疫法测定了犬离体动脉中血栓素B_2(TXB_2)的释放量。脑动脉、冠状动脉、肠系膜动脉和隐动脉释放的TXB 2量分别为47.0 ± 7.2、4.0 ± 0.6、4.9 ± 0.5和2.7 ± 0.4 pg/mg湿重组织/30 min。给药吲哚美辛(10 ~(-5)M)或OKY-046(10 ~(-4)M)和摩擦内膜可使脑动脉释放的TXB_2降至<5%。在培养基中加入花生四烯酸(AA)(10 ~(-5)M)可使TXB_2的释放增加近2倍,而加入乙酰胆碱(ACh)(10 ~(-6)M)则无此作用。脑动脉条保持静息张力,罂粟碱(10-4 M)最大限度地降低。环氧合酶抑制剂(吲哚美辛)、血栓烷A2(TXA 2)合成酶抑制剂(OKY-046)和TXA 2拮抗剂(ONO-3708)也可剂量依赖性地降低静息张力。摩擦条的静止色调约为完整条的一半。ACh和AA引起类似的短暂收缩脑动脉。消炎痛(10-7 M)、阿司匹林(5 × 10-5 M)、OKY-046(10-6 M)和ONO-3708(10-8 M)可减弱这些药物引起的收缩,摩擦内膜可消除这些收缩。从这些结果可以得出结论,TXA 2是在内皮细胞中产生的,并可能参与维持静息张力和收缩反应AA在犬脑动脉。
Summary The amount of immunoreactive thromboxane B2 (TXB2) released from isolated canine arteries was determined by radioimmunoassay. The amount of TXB2 released from the cerebral, coronary, mesenteric, and saphenous arteries was 47.0 ± 7.2, 4.0 ± 0.6, 4.9 ± 0.5, and 2.7 ± 0.4 pg/mg wet weight tissue/30 min, respectively. The release of TXB2 from the cerebral artery was decreased to <5% by the administration of indomethacin (10-5 M) or OKY-046 (10-4 M), and by intimal rubbing. The release of TXB2 was enhanced nearly twofold by the addition of arachidonic acid (AA) (10-5 M) to the medium, but not by the addition of acetylcholine (ACh) (10-6 M). The cerebral arterial strips maintained the resting tone, which was reduced maximally by papaverine (10-4 M). The resting tone was also reduced dose dependently by a cyclooxygenase inhibitor (indomethacin), a thromboxane A2 (TXA2) synthetase inhibitor (OKY-046), and a TXA2 antagonist (ONO-3708). The resting tone of rubbed strips was about half that of intact strips. ACh and AA induced similar transient contractions in the cerebral artery. Contractions produced by these agents were attenuated by indomethacin (10-7 M), aspirin (5 × 10-5 M), OKY-046 (10-6 M), and ONO-3708 (10-8 M), and abolished by intimal rubbing. From these results, it is concluded that TXA2 is produced in the endothelial cells and may be involved in maintaining the resting tone and contractile response to AA in the canine cerebral artery.