ASPIRIN CAUSES SHORT-LIVED INHIBITION OF BRADYKININ-STIMULATED PROSTACYCLIN PRODUCTION IN MAN
ASPIRIN CAUSES SHORT-LIVED INHIBITION OF BRADYKININ-STIMULATED PROSTACYCLIN PRODUCTION IN MAN
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DOI：
10.1038/318186a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
RITTER, JM
中科院分区：
文献类型：
--
作者：
HEAVEY, DJ;BARROW, SE;RITTER, JM
乙酰水杨酸（阿司匹林）通过脂肪酸环氧合酶的不可逆乙酰化作用抑制前列腺素类合成1，2（EC 1.14.99.1）3。因此，它抑制血小板合成促聚集血栓素A2（TXA 2）2，4，并广泛用于治疗和预防血管疾病。然而，其疗效可能会降低，因为它也抑制前列环素（PGI 2）的形成5，6这是一种血管扩张剂和抗聚集剂7，8。阿司匹林的最佳剂量方案尚不确定，因为尽管它可抑制血小板血栓素的产生达数天4，但其对体内血管内皮细胞产生PGI 2的影响程度和持续时间尚不清楚。PGI 2的静息血浆浓度（以稳定水解产物6-oxo-PGF 1 α形式测定）等于或低于最灵敏测定的灵敏度限度9，因此不能用于证明产量降低。缓激肽通过培养的人血管内皮细胞刺激PGI 2的合成10，我们已经证明缓激肽通过体内的人刺激PGI 2的产生11。我们在此报告，口服阿司匹林（600 mg）可迅速和实质性抑制缓激肽刺激的PGI 2生成，但在6小时内恢复;这意味着，即使是这种相对较大剂量的阿司匹林，每日一次给药期间，大部分时间内内皮细胞PGI 2的合成也不会受到影响。
Acetylsalicyclic acid (aspirin) inhibits prostanoid synthesis1,2by irreversible acetylation of fatty acid cyclooxygenase (EC 1.14.99.1)3. It thereby inhibits synthesis of pro-aggregatory thromboxane A2(TXA2) by platelets2,4and is widely used in the treatment and prophylaxis of vascular disease. Its efficacy, however, may be reduced since it also inhibits formation of prostacyclin (PGI2)5,6which is a vasodilator and anti-aggregatory agent7,8. There is uncertainty over the optimum dose regimen for aspirin since although it inhibits platelet thromboxane production for many days4, the magnitude and duration of its effect on PGI2production by vascular endotheliumin vivois unknown. Resting plasma concentrations of PGI2(measured as the stable hydrolysis product 6-oxo-PGF1α) are at or below the limit of sensitivity of the most sensitive assays9and cannot therefore be used to demonstrate a reduction in production. Bradykinin stimulates PGI2synthesis by cultured human vascular endothelial cells10and we have shown that it stimulates PGI2production by manin vivo11. We report here that an oral dose of aspirin (600 mg) causes rapid and substantial inhibition of bradykinin-stimulated PGI2production, but recovery occurs within 6 hours; this implies that endothelial PGI2synthesis would be spared most of the time during dosing once daily with even this relatively large dose of aspirin.