Biotransformation and cardiovascular effects of arachidonic acid in the dog.
Biotransformation and cardiovascular effects of arachidonic acid in the dog.
复制标题
花生四烯酸在狗体内的生物转化和心血管作用。
DOI：
10.1016/0014-2999(79)90080-3
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发表时间：
1979
影响因子：
5
通讯作者：
J. Vane
中科院分区：
文献类型：
--
作者：
K. Mullane;G. Dusting;J. Salmon;S. Moncada;J. Vane
本文研究了花生四烯酸（AA）在麻醉犬循环中的生物转化和心血管效应。使用Vane的血浴器官技术连续生物测定动脉血中的花生四烯酸代谢物。将AA（5-10 μ g/ml）注入流动血液的孵育线圈中，可使血管组织（兔主动脉，RbA，兔腹腔动脉和肠系膜动脉，RbCA和RbMA，牛冠状动脉，BCA）和胃肠平滑肌条（大鼠胃条，RSS，大鼠结肠，RC）收缩。这些作用可以通过外源性产生的血栓素A2（TXA2）来模拟。吲哚美辛和选择性血栓素合成酶抑制剂咪唑（100 μ g/ml）可抑制AA的转化。TXA2在血液中的半衰期为30 - 47秒，与37 ° C下水溶液中的半衰期相似。PGH_2在血液中也可转化为其他产物，收缩RSS和RC，舒张RbCA和RbMA，但对RbA影响不大。静脉输注AA（50 - 800 μ g kg − 1min − 1）对生物测定组织产生影响，前列环素可模拟这种影响。AA输注还诱导肺动脉和全身动脉压的福尔斯下降和心动过缓。吲哚美辛（5 mg/kg）或阿司匹林（200 mg/kg）可消除上述效应。放射免疫分析证实，静脉输注AA的主要产物是前列环素的化学降解产物6-oxo-PGF 1 α。因此，尽管AA在单独与血液孵育足够时间后转化为血管收缩剂TXA2，但在快速肺转运时，它转化为前列环素样物质。
The biotransformation and cardiovascular effects of arachidonic acid (AA) were studied in the circulation of anaesthetized dogs. Arterial blood was continuously bioassayed for arachidonate metabolites using the blood-bathed organ technique of Vane. AA (5–10 μg/ml) infused into an incubation coil of flowing blood was converted into a labile substance which contracted the vascular tissues (rabbit aorta, RbA, rabbit coeliac and mesenteric arteries, RbCA and RbMA; bovine coronary artery, BCA) and the gastrointestinal smooth muscle strips (rat stomach strip, RSS; rat colon, RC). These effects could be mimicked by exogenously generated thromboxane A2(TXA2). Conversion of AA was inhibited by indomethacin and the selective thromboxane synthetase inhibitor, imidazole (100 μg/ml). The half-life of TXA2in blood was 30–47 sec, a similar value to that found in aqueous solutions at 37°C. PGH2was also converted in blood to other product(s) which contracted RSS and RC, relaxed RbCA and RbMA but had little effect on RbA. Intravenous infusion of AA (50–800 μg kg−1min−1) caused effects on the bioassay tissues which could be mimicked by prostacyclin. The AA infusion also induced falls in pulmonary and systemic arterial pressures and bradycardia. All effects were abolished by indomethacin (5 mg/kg) or aspirin (200 mg/kg). Radioimmunoassay confirmed that the major product of intravenously infused AA was 6-oxo-PGF1α, the chemical degradation product of prostacyclin. Thus, although AA is transformed to the vasoconstrictor TXA2when incubated for sufficient time with blood alone, on rapid pulmonary transit it is transformed into a prostacyclin-like substance.