Exogenous tetrahydrobiopterin causes endothelium-dependent contractions in isolated canine basilar artery.
Exogenous tetrahydrobiopterin causes endothelium-dependent contractions in isolated canine basilar artery.
复制标题
外源性四氢生物蝶呤引起离体犬基底动脉的内皮依赖性收缩。
DOI：
10.1152/ajpheart.1996.271.2.h738
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Katusic,ZS
中科院分区：
文献类型：
--
作者：
Kinoshita,H;Katusic,ZS
四氢生物蝶呤是一氧化氮生物合成中必不可少的辅因子，但在氧气存在的情况下，四氢生物蝶呤的自氧化会导致超氧阴离子的产生，进而导致一氧化氮的化学失活。因此，本实验旨在确定外源性四氢生物蝶呤对犬离体基动脉的作用。将有内皮和无内皮的环悬挂在改良的Krebs-Ringer碳酸氢盐溶液中，用94%O2-6%CO2(37℃；pH 7.4)起泡，记录等长力。用放射免疫法测定3‘，5’环一磷酸鸟苷产量(CGMP)。四氢生物蝶呤(10(-7)~10(-4)M)引起内皮依赖性收缩，而不是二氢生物蝶呤或生物蝶呤。超氧化物歧化酶(150U/ml)可阻断四氢生物蝶呤引起的收缩，但过氧化氢酶(1200U/ml)和羟基自由基清除剂去铁胺(10(-4)M)和二甲基亚砜(10(-4)~10(-3)M)对四氢生物蝶呤引起的收缩无明显影响。环氧合酶抑制剂吲哚美辛(10(-5)M)显著降低四氢生物蝶呤的收缩作用。在前列腺素H2/血栓素A2受体拮抗剂SQ-29548(10(-6)M)存在下，收缩逆转为松弛。在有内皮的血管环中，四氢生物蝶呤(10(-4)M)显著降低cGMP水平。这些研究表明，外源性四氢生物蝶呤的自氧化通过1)超氧阴离子化学灭活一氧化氮和2)通过环氧合酶途径激活花生四烯酸代谢，从而从内皮细胞释放内源性过氧化物质和/或血栓素A2，从而诱导内皮依赖性收缩。
Tetrahydrobiopterin is an essential cofactor in the biosynthesis of nitric oxide, but in the presence of O2, autooxidation of tetrahydrobiopterin leads to the production of superoxide anions and the subsequent chemical inactivation of nitric oxide. As a result, the present experiments were designed to determine the effect of exogenous tetrahydrobiopterin on isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric force recording in modified Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C; pH 7.4). A radioimmunoassay technique was used to measure guanosine 3',5' cyclic monophosphate production (cGMP). Tetrahydrobiopterin (10(-7) to 10(-4) M), but not dihydrobiopterin or biopterin, caused endothelium-dependent contractions. Superoxide dismutase (150 U/ml) abolished tetrahydrobiopterin-induced contractions, but a H2O2 scavenger, catalase (1,200 U/ml), and hydroxyl radical scavengers deferoxamine (10(-4) M) and dimethylsulfoxide (10(-4) to 10(-3) M) did not significantly affect the contractions. A cyclooxygenase inhibitor, indomethacin (10(-5) M), significantly reduced the contractile effect of tetrahydrobiopterin. With the prostaglandin H2/ thromboxane A2 receptor antagonist, SQ-29548 (10(-6) M) present, contractions reversed to relaxations. In rings with endothelium, tetrahydrobiopterin (10(-4) M) significantly decreased the levels of cGMP. These studies suggest that autooxidation of exogenous tetrahydrobiopterin induces endothelium-dependent contractions by 1) chemical inactivation of nitric oxide by superoxide anions and 2) activation of arachidonic acid metabolism via the cyclooxygenase pathway with subsequent release of endoperoxide and/or thromboxane A2 from endothelial cells.