Belch J J, Small M, McKenzie F, Hill P A, Lowe G D, McIntyre D E, Forbes C D, Prentice C R
Thromb Haemost. 1982 Apr 30;47(2):122-3.
Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
去氨基-D-精氨酸血管加压素（DDAVP）可刺激血管内皮释放因子VIII和纤溶酶原激活物。给血友病患者输注外源性因子VIII会导致血小板活化增加。而在通过输注DDAVP使患者自身因子VIII水平升高后，这种活化并未发生。因此我们推测，DDAVP还可促使内皮释放前列环素（PGI2），这是一种强效抗血小板剂，可抵消因子VIII的聚集作用。为检验这种可能性，我们研究了DDAVP对前列环素释放的影响，通过其稳定代谢产物6-氧代-PGF1α在体外和体内进行测定。将兔主动脉环与不同浓度的DDAVP一起孵育，以生理盐水作为对照。通过放射免疫分析法检测上清液中的6-氧代-PGF1α。所有浓度的DDAVP均使6-氧代-PGF1α显著释放。血管加压素的作用则弱得多。当给血友病患者输注DDAVP后，输注后即刻循环中的6-氧代-PGF1α水平显著升高。因此，作为DDAVP副作用观察到的面部潮红可能是由前列环素介导的。我们通过预先用阿司匹林治疗来消除正常受试者中DDAVP诱导的潮红，从而证实了这一点，阿司匹林可抑制PGI2的形成。
