Belo S E, Talesnik J
Br J Pharmacol. 1982 Feb;75(2):269-86. doi: 10.1111/j.1476-5381.1982.tb08783.x.
The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25 mg/1) reversibly inhibited both phases of the response induced by AA. Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. Short infusions of acetylsalicylic acid at low concentrations (2.9 micrograms/ml), dipyridamole (0.6 micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively inhibited the vasoconstrictor phase of the response to AA. It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. Linolenic, linoleic, dihomo-gamma-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.
给大鼠离体灌流心脏给予花生四烯酸（AA）通常会产生双相性冠状动脉反应，其特征为最初的血管收缩，随后是长时间的血管舒张。然而，有些反应主要是血管收缩或血管舒张。非甾体抗炎药（NSAA）吲哚美辛（1 - 5毫克/升）和萘普生（12.5 - 25毫克/升）可可逆地抑制AA诱导反应的两个阶段。每天用吲哚美辛（5毫克/千克）或萘普生（25毫克/千克）预处理动物，导致对AA的冠状动脉反应未改变。随后向灌流液中添加NSAA可抑制AA的作用。低浓度（2.9微克/毫升）的乙酰水杨酸、双嘧达莫（0.6微克/毫升）和磺吡酮（28.7微克/毫升）的短时间输注选择性地抑制了对AA反应的血管收缩阶段。已证实心脏刺激诱导的代谢性冠状动脉舒张会被长时间给予AA所抑制；NSAA预处理可防止这种作用。NSAA对冠状动脉短暂阻塞后的反应性充血反应无影响。亚麻酸、亚油酸、二高 - γ - 亚麻酸和油酸通常会使冠状动脉血流量减少，NSAA、双嘧达莫或磺吡酮对此无影响。在完整大鼠中，主动脉内注射AA、前列环素（PGI2）和前列腺素E2（PGE2）会使血压呈剂量依赖性下降，吲哚美辛可抑制AA的反应。PGI2和PGE2在离体心脏中产生持久的冠状动脉舒张。AA的冠状动脉作用似乎是由于其在易于接近的血管壁内转化为前列腺素和血栓素样物质。我们认为一种血管收缩性血栓素A2样物质可能是冠状动脉痉挛的原因。冠状动脉供血不足也可能是由于心肌细胞内PGE2合成增加抑制了代偿性代谢性冠状动脉舒张所致。
