Pagano P J, Lin L, Sessa W C, Nasjletti A
Department of Pharmacology, New York Medical College, Valhalla 10595.
Circ Res. 1991 Aug;69(2):396-405. doi: 10.1161/01.res.69.2.396.
This study was designed to investigate the mediator(s) of endothelium-dependent arterial constrictor responses evoked by arachidonic acid in vitro. A segment of descending rabbit thoracic aorta was isolated and perfused (1-2 ml/min) with oxygenated Krebs' bicarbonate buffer. Changes in the vascular smooth muscle-contracting activity of the aortic effluent were detected by superfusion bioassay using either strips of rabbit aorta or rings of dog saphenous vein, both denuded of endothelium and exposed to indomethacin (10 microM). Arachidonic acid (5-50 micrograms) injected into the inflow of the perfused aorta caused a dose-related increase in the vascular smooth muscle-contracting activity of the aortic effluent, whereas arachidonic acid added directly into the aortic effluent did not. The arachidonic acid-induced elevation of vascular smooth muscle-contracting activity in the aortic effluent was not apparent when indomethacin (10 microM) was added to the aortic inflow to inhibit cyclooxygenase, when the endothelium of the perfused aorta was removed by rubbing, or when the thromboxane A2/prostaglandin H2 receptors of the vascular tissues used for bioassay were blocked with an antagonist (1 microM SQ29548), and was unaffected when an inhibitor of thromboxane synthase (10 microM CGS 13080) was added to the aortic inflow. This effect of arachidonic acid was accompanied by release of prostaglandin H2 (measured as prostaglandin F2 alpha after reduction with SnCl2) in amounts sufficient to elicit contraction of the vascular tissues used for bioassay and was attenuated when a reducing agent (2 mM FeCl2) that converts prostaglandin H2 to 12-heptadecatrienoic acid was added to the aortic effluent. Collectively, these observations suggest that arachidonic acid stimulates endothelium-dependent release from the perfused aorta of a prostanoid that contracts vascular smooth muscle via interaction with thromboxane A2/prostaglandin H2 receptors. The study also suggests that the prostanoid responsible for the vascular smooth muscle-contracting activity of the aortic effluent is a prostaglandin endoperoxide(s) rather than thromboxane A2.
本研究旨在调查体外花生四烯酸诱发的内皮依赖性动脉收缩反应的介质。分离一段兔胸主动脉降段，并用充氧的 Krebs 碳酸氢盐缓冲液（1 - 2 ml/分钟）进行灌注。使用兔主动脉条或犬隐静脉环通过超灌流生物测定法检测主动脉流出液中血管平滑肌收缩活性的变化，两者均去除内皮并暴露于吲哚美辛（10 μM）。注入灌注主动脉流入端的花生四烯酸（5 - 50 μg）导致主动脉流出液中血管平滑肌收缩活性呈剂量相关增加，而直接添加到主动脉流出液中的花生四烯酸则无此作用。当向主动脉流入端添加吲哚美辛（10 μM）以抑制环氧化酶时，当通过摩擦去除灌注主动脉的内皮时，或当用于生物测定的血管组织的血栓素 A2/前列腺素 H2 受体被拮抗剂（1 μM SQ29548）阻断时，花生四烯酸诱导的主动脉流出液中血管平滑肌收缩活性升高不明显，并且当向主动脉流入端添加血栓素合酶抑制剂（10 μM CGS 13080）时不受影响。花生四烯酸的这种作用伴随着前列腺素 H2 的释放（用 SnCl2 还原后测定为前列腺素 F2α），其释放量足以引起用于生物测定的血管组织收缩，并且当向主动脉流出液中添加将前列腺素 H2 转化为 12 - 十七碳三烯酸的还原剂（2 mM FeCl2）时减弱。总体而言，这些观察结果表明，花生四烯酸刺激灌注主动脉释放一种前列腺素，该前列腺素通过与血栓素 A2/前列腺素 H2 受体相互作用使血管平滑肌收缩。该研究还表明，负责主动脉流出液中血管平滑肌收缩活性的前列腺素是前列腺素内过氧化物而非血栓素 A2。
