The purpose of this study was to clarify the role of the platelet activating factor (PAF) in the pathophysiology of preeclampsia.
1) Plasma levels of PAF and PAF-acetylhydrolase activity (PAF-AH), which is an enzyme metabolizing PAF into an inactive form, were determined in normal and hypertensive pregnancy. Plasma concentrations of PAF in normal male and non-pregnant women in the follicular phase and luteal phase were 653.7, 488. 8 and 620.2 pg/ml, respectively. Those in normal pregnant women in the 1st, 2nd and 3rd trimester and puerperal subjects were 291.7, 242.9, 246.4 and 256.2 pg/ml, respectively. Plasma PAF in normal pregnant women was significantly lower than that in nonpregnant subjects. Plasma concentrations of PAF-AH in normal male and non-pregnant women in follicular phase and luteal phase were 31.1, 21.1 and 22.2 nmol/ min/ml, respectively. Those in normal pregnant women in 1st, 2nd and 3rd trimester and puerperal subjects were 18.1, 18.0, 18.8 and 19.3 nmol/min/ml, respectively. Plasma PAF-AH in normal pregnant women tended to be lower than that in nonpregnant subjects, while the difference between them was not statistically significant. Plasma levels of PAF in mild and severe preeclamptic patients were 295.2 and 426.0 pg/ ml, respectively. Either level was significantly higher than that in normal pregnant women in the 3rd trimester. Plasma levels of PAF-AH in mild and severe preeclamptic subjects were 17.3 and 13.8 nmol/min/ ml, respectively. PAF-AH in patients with severe preeclampsia was significantly lower compared with that in women with normal pregnancy in the 3rd trimester. In preeclamptic patients a negative correlationship between plasma concentrations of PAF and PAF-AH was noted, but not in normal pregnant women.
2) Relationships between plasma levels of PAF and either of several parameters in physiology were investigated. There was a negative correlationship between plasma PAF concentrations and diastolic blood pressure in mild and severe preeclamptic patients, while no such correlation was noted in normal pregnant women. The platelet count in peripheral blood of preeclamptic women was significantly correlated to plasma PAF levels, but not in normal pregnant subjects. There was a weak correlationship between hematocrit and plasma PAF levels in normal pregnant women, however, but not in preeclamptic women.
3) According to
in vitro experiments using cultured human umbilical endothelial cells, sera obtained from preeclamptic subjects displayed more potential toward an increase in intracellular PAF production than did the samples from normal pregnant women. However, PAF release into media of the cultured cell was not affected by the preeclamptic sera. Estradiol and progesterone had a small inhibitory effect in intracellular PAF production. The former also inhibited the PAF release into media, while the latter stimulated it. However, these changes which caused the steroids in either the PAF production or release were not enough to explain the alteration in PAF concentration in preeclamptic women compared to normal pregnant women. Prolactin and parathyroid hormone (PTH) increased the intracellular PAF production, while human placental lactogen (hPL) had the smallest effect on that. Prolactin and hPL did not cause any changes in PAF release into media, although PTH increased the compound release.
These results suggest the following :
1) In preeclamptic patients PAF may have a role in antagonizing hypertension, which is considered to be one of the homeostatic functions against the pathophysiology.
2) Sera from preeclamptic women may contain factors which stimulate PAF production. PTH seems to be one of humoral factors which are responsible for such stimulatory effects.
3) PAF is regarded as not a causative, but a modulating factor in preeclampsia. [Adv Obster Gynecol 46(2) : 163-186, 1994 (H6.3)]
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