Mileikowsky G N, Nadler J L, Huey F, Francis R, Roy S
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Am J Obstet Gynecol. 1988 Dec;159(6):1547-52. doi: 10.1016/0002-9378(88)90592-3.
Smoking markedly intensifies the risk of cardiovascular disease in women who use oral contraceptives. The mechanism of this effect is not known, but evidence in vitro and in male smokers suggests that nicotine and cigarette smoke can alter prostaglandin formation and platelet function. However, these effects had not been studied with regard to women. We evaluated the effects of smoking on prostacyclin formation and platelet aggregation in 38 women who were matched according to age and weight. These included 24 women who used oral contraceptives (15 smokers, 9 nonsmokers) and 7 smokers who did not use oral contraceptives. In addition, a control group comprised seven healthy, nonsmoking women who did not take oral contraceptives. Prostacyclin formation, reflected by the excretion rate of its stable metabolite 6-keto-prostaglandin F1 alpha, was measured by means of radioimmunoassay in 4-hour urine specimens obtained during a smoking-free period and after participants had inhaled smoke from four high-nicotine cigarettes. In addition, ex vivo platelet aggregation in response to adenosine diphosphate and the stable thromboxane/endoperoxide analog U 46619 was evaluated before and after the inhalation of cigarette smoke. Oral contraceptive users who smoked greater than or equal to 5 years had a lower basal 6-keto-prostaglandin F1 alpha level than nonsmokers or those with a smoking history of less than 5 years (84 +/- 11 versus 159 +/- 28 versus 171 +/- 18 ng/gm of creatinine, p less than 0.01). Inhalation of smoke from four high-nicotine cigarettes did not alter 6-keto-prostaglandin F1 alpha in the smokers who did not use oral contraceptives. However, excretion of 6-keto-prostaglandin F1 alpha was further reduced in the smokers who used oral contraceptives (133 +/- 20 to 86 +/- 9 ng/gm of creatinine, p less than 0.05). Platelet aggregation did not change after inhalation of cigarette smoke in the women who did not take oral contraceptives, but aggregation increased in participants who used oral contraceptives. These results suggest that prostacyclin inhibition may be an important mechanism for the increased cardiovascular risk in women smokers who take oral contraceptives.
吸烟会显著增加服用口服避孕药的女性患心血管疾病的风险。这种效应的机制尚不清楚，但体外实验和男性吸烟者的证据表明，尼古丁和香烟烟雾会改变前列腺素的形成和血小板功能。然而，这些效应在女性中尚未得到研究。我们评估了吸烟对38名年龄和体重匹配的女性前列环素形成和血小板聚集的影响。其中包括24名服用口服避孕药的女性（15名吸烟者，9名不吸烟者）和7名不服用口服避孕药的吸烟者。此外，一个对照组由7名健康、不吸烟且不服用口服避孕药的女性组成。通过放射免疫分析法，在无烟期以及参与者吸入四根高尼古丁香烟后采集的4小时尿液样本中，测量前列环素的形成，以前列环素稳定代谢物6-酮-前列腺素F1α的排泄率来反映。此外，在吸入香烟烟雾前后，评估了对二磷酸腺苷和稳定的血栓素/内过氧化物类似物U 46619的体外血小板聚集情况。吸烟≥5年的口服避孕药使用者的基础6-酮-前列腺素F1α水平低于不吸烟者或吸烟史少于5年的使用者（分别为84±11、159±28和171±18 ng/g肌酐，p<0.01）。吸入四根高尼古丁香烟的烟雾后，不服用口服避孕药的吸烟者的6-酮-前列腺素F1α没有改变。然而，服用口服避孕药的吸烟者的6-酮-前列腺素F1α排泄进一步减少（从133±20降至86±9 ng/g肌酐，p<0.05）。不服用口服避孕药的女性吸入香烟烟雾后血小板聚集没有变化，但服用口服避孕药的参与者的血小板聚集增加。这些结果表明，前列环素抑制可能是服用口服避孕药的女性吸烟者心血管风险增加的重要机制。
