Influence of a cigarette smoke extract on the hormonal regulation of platelet-activating factor acetylhydrolase in rats.

We evaluated the effects of estrogen, progestin, and cigarette smoke extract (CSE) on plasma platelet-activating factor (PAF) acetylhydrolase (AH; PAF-AH) activity in rats. The effects on rat tissues of an i.v. injection of PAF were studied as part of our investigation of the mechanisms involved in thrombotic episodes. Plasma PAF-AH activity in adult female rats (14 wk of age) treated with 17 alpha-ethynylestradiol (100 micrograms/kg, 5 days) was decreased by 70%. Medroxyprogesterone (50 mg/kg, 5 days) increased PAF-AH activity by 50%. CSE (0.5 cigarette/kg, 5 days) did not alter PAF-AH activity during the treatment. However, a combination of CSE and 17 alpha-ethynylestradiol decreased plasma PAF-AH activity by 90%. The decrease in PAF-AH activity was age-dependent. The effect of medroxyprogesterone on plasma PAF-AH activity was not influenced by CSE. When PAF (5-40 nmol/kg) was injected i.v. into untreated adult female rats, 9 of 16 animals died after a 20-nmol/kg dose of PAF. Macroscopic findings included hemorrhage, hyperemia, and congestion in the lungs and heart, and necrosis-like changes in the gastrointestinal tract. Microscopically, thrombi were observed in the lungs and heart. When PAF was administered to adult female rats pretreated with sex steroid hormones, the mortality of rats with low plasma PAF-AH activity caused by 17 alpha-ethynylestradiol was increased but that of rats with high PAF-AH activity caused by medroxyprogesterone was decreased. Thus, PAF and PAF-AH may play important roles in the thrombotic episodes known to occur in female smokers who use oral contraceptives.