Plasma renin activity , plasma concentratrions of angiotensin 11(AngII), stable metabolites (6-keto-prostaglandin Fla : 6-keto-PGFIa) of prostacyclin (PGI2) and a metabolite (thromboxane B2: TXB2) of thromboxane A2 (TXA2 ) were measured with radioimmunoassay(RIA) in 107 normal pregnancy (control) and 139 preeclamptic patients in 28-41 gestational weeks. PRA and 6-ketoPGFIa were significantly higher and AngII was slightly higher in preeclampsia than in control, and TXB2 was significantly lower in preeclampsia in control. The ratio of 6-keto-PGFIa/TXB2 was significantly lower in preeclampsia than in control. These data suggest that the changes in the renin-angiotensin system may not be primary alterations in preeclampsia. It can be speculated that in preeclampsia the changes in absolute concentrations of 6-keto-PGFIa and TXB2 are less important than the decrease in the ratio of the 6-keto-PGFIa/TXB2. plasma renin activity ; angiotensin II ; prostacyclin ; tromboxane A2; preeclampsia The renin-angiotensin system is known to play an important role in the maintenance of normal blood pressure and it has been shown that women who have, or are destined to develop, preeclampsia show an increased sensitivity to infused angiotensin II (Gant et al. 1976). This effect can be abolished by the administration of prostaglandin E2 or induced by the prior administration of an inhibitor of prostaglandin synthetase (Everetta et al. 1978). It is well established that vasocon-striction in the arteriolar bed, particularly in the uterus and kidney, is a characteristic feature of preeclampsia. Thromboxane A2 (TXA2) and prostacyclin (PGI2) are potent vasoactive compounds. TXA2 causes vasoconstriction and induces platelet aggregation, whereas PGI2 has the opposite properties (Moncada and Vane 1978). Other studies with isolated tissues have shown that there

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclapmsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGFIa (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 + 3.8 pg/ml, mean+ s.E.) and also umbilical plasma ANP (n = 35, 83.0± 4.2 pg/ml) were significantly (p <0.01) higher than those of normal pregnant women plasma (n=19, 58.7± 3.7 pg/ml) and umbilical plasma (n =19, 47.6±4.7 pg/ml ). There was a significant (p <0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGFIa levels in preeclampsia were significantly (p <0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGFIa/TXB2 in preeclampsia was significantly (p <0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGFI a concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.atrial natriuretic peptide ; plasma renin activity ; preeclampsia ; Prostacyclin ; thromboxane A2 Atrial natriuretic peptide (ANP) is a peptide, synthesized and released from

Recently, nifedipine (Ca antagonist) has been used for the treatment of preeclampsia. In this study, we investigated the effects of nifedipine on the normotensive Wistar Kyoto rat’s placental blood flow, fetal weight and placental weight. We measured the rat’s placental blood flow using clearance of hydrogen gas generated by electrolysis. The placental blood flow, placental and fetal weights of nifedipine-treated rats (5, 10 and 25 mg/kg) were significantly (p < 0.05) reduced compared with normal pregnant rats. These data suggest that nifedipine might have some reducing effects on placental blood flow, fetal weight and placental weight.

Recently, ketanserin (serotonin receptor antagonist) has been reported to be beneficial in the treatment of preeclampsia. In this study, we investigated the effects of ketanserin on the placental blood flow, fetal weight and placental weight in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). We measured the rats’ placental blood flow by monitoring the clearance of hydrogen gas generated by electrolysis. In ketanserin (12, 24, 48 mg/kg)-treated SHR, systolic blood pressure was significantly decreased. The placental blood flow was significantly (p < 0.05) reduced compared to that before treatment in WKY and SHR. The fetal weight decreased dose dependently in WKY, while in SHR it did not decrease significantly. The placental weight of ketanserin-treated rats decreased compared to that before treatment. These data suggest that ketanserin might have some reducing effects on placental blood flow, fetal weight and placental weight proportional to the dose.

In this study, we present our initial trials in the treatment of 6 cases of severe preeclampsia with thromboxane synthetase inhibitor (OKY-046). Following the treatment with OKY-046, maternal systolic blood pressure decreased significantly and umbilical artery waveforms were normalized. These data suggest that thromboxane synthetase inhibition might have a beneficial effect on preeclampsia.