prostaglandin-h2 and Pre-Eclampsia

Pregnancy induced hypertension (PIH) is associated with a variety of disturbances in the hemostatic system including alterations in platelet function, thrombocytopenia, and an increase in platelet turnover. The density of platelet Thromboxane A2 (TXA2)/Prostaglandin H2 (PGH2) receptors was determined in patients with PIH and normal pregnant women, using [125I]-PTA-OH, a TXA2/PGH2 receptor antagonist. The number of platelet TXA2/PGH2 receptors significantly increased (p < 0.008) from 1734 +/- 370 sites/platelet (n = 8) in normal pregnant women to 3703 +/- 846 sites/platelet (n = 9) in patients with severe PIH. The sensitivity of platelets to the TXA2 mimetic U46619 was significantly (p < 0.0005) increased in platelets obtained from severe PIH patients (EC50 = 150 +/- 10nM, n = 3) compared to controls (EC50 = 290 +/- 60 nM, n = 5). These results indicate that an increased number of TXA2/PGH2 receptors as well as increased sensitivity to TXA2/PGH2 mimetics occurs in PIH. Collectively, these results provide further support for the notion that TXA2 and its receptor may play an important role in the pathophysiology of PIH.

Topics: Blood Platelets; Female; Humans; Platelet Aggregation; Platelet Count; Pre-Eclampsia; Pregnancy; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Receptors, Prostaglandin; Receptors, Thromboxane; Receptors, Thromboxane A2, Prostaglandin H2; Severity of Illness Index; Thromboxane A2

Characterization of the PGI2 producing enzyme system (P.E.S.) in pregnancy induced hypertension (PIH) was carried out by comparing its conversion from arachidonic acid (A.A.) or PGH2 to PGI2 using enzyme preparations from endothelial cells of the umbilical vein in normal pregnancy (N) and mild (M) and severe (S) types of PIH. 1) The conversion rate from A.A. to PGI2 in N was significantly (p less than 0.05) higher than in M and S. 2) The conversion rate from PGH2 to PGI2 in N was higher than in M and that in M was higher than in S. 3) The apparent Vmax values (nM/mg protein) (mean +/- S.E.M.) for P.E.S. in N (0.88 +/- 0.21) were significantly (p less than 0.05) lower than in M (2.76 +/- 0.71) and S (1.63 +/- 0.18). The apparent Km values (microM) (mean +/- S.E.M.) for P.E.S. in N (0.76 +/- 0.25) were significantly (p less than 0.05) higher than in M (0.29 +/- 0.07) and significantly (p less than 0.05) lower than in S (3.26 +/- 0.78). 4) The apparent Vmax values for PGI2 synthetase (P.S.) in N (0.44 +/- 0.09) and M (0.61 +/- 0.10) were significantly (p less than 0.05) higher than in S (0.11 +/- 0.06). The apparent Km values for P.S. in N, M and S were 0.12 +/- 0.07, 0.13 +/- 0.06 and 0.16 +/- 0.04, respectively. The present study showed that the symptoms in M may be kept from becoming aggravated by the production of large amounts of PGI2, due mainly to activation of cyclooxygenase, whereas progressive disorder of the regulation of blood pressure in S may be caused by low production of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Cytochrome P-450 Enzyme System; Endothelium, Vascular; Epoprostenol; Female; Humans; Intramolecular Oxidoreductases; Isomerases; Pre-Eclampsia; Pregnancy; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandin-Endoperoxide Synthases; Prostaglandins H; Umbilical Veins