In vitro activity of nicotinamide adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-linked 15-hydroxyprostaglandin dehydrogenases in placentas from normotensive and preeclamptic/eclamptic pregnancies.

Abstract

Concentrations of prostaglandins E2 and I2 may be decreased in preeclamptic and eclamptic pregnancies. Because these prostaglandins produce vasodilation and inhibit platelet aggregation it has been suggested that a reduction in their biosynthesis might play an important role in the pathogenesis of the hypertension and coagulation abnormalities associated with preeclampsia. Placental tissue is an extremely rich source of several enzymes that catalyze the catabolism of prostaglandins. The present study was initiated to determine whether one of these catabolic enzymes might be increased in preeclamptic/ eclamptic pregnancies. The activities of the NAD-and the NADP-linked 15-hydroxyprostaglandin dehydrogenases were measured in 16 preeclamptics (mean diastolic pressure, 108±13 mmHg) and compared with 16 normotensive controls matched for age (20.8±5.43 vs. 20.6±5.16) and gestational week of delivery (34.6±5.40 vs. 35.0±5.06). These results indicate that the activity of the placental NAD-linked 15-hydroxyprostaglandin dehydrogenase is elevated in preeclampsia (40.1±31.3 vs. 14.9±8.30 mU/g tissue, P < 0.01). If this increase were also expressed in vivo, its effect on prostaglandin metabolism could be mistaken for impaired prostacyclin biosynthesis unless both the 6-keto-and 6,15-diketo-metabolites of prostacyclin were measured.

Gene Expression Profiling of Placentas Affected by Pre-Eclampsia

“…One study has found a twofold reduction of PGDH mRNA levels in placental tissue of patients with pre-eclampsia, compared with matched controls [ 24 ]. Others have found an increase in the activity of PGHD in pre-eclamptic placentas [ 25 ]. We found an upregulation (1.48-fold) of PGDH in the pre-eclamptic placentas.…”

Nifedipine Increases Urinary Excretion of Prostacyclin Metabolite in Hypertensive Pregnancy

“…Imbalance of the vasoconstrictive and vasodilatory prostanoids has been reported to be associated with the pathophysiology of hypertensive pregnancy, possibly due to deficiency of formation or increased metabolism of vasodilatory prostaglandins (Jarabak et al 1987), or increased production of thromboxane A, (TXA,) (Walsh 1985). The TXA,/prostacyclin (PGI,) ratio is increased in maternal and umbilical venous plasma (Yamaguchi & Mori 1985), in amniotic fluid (Ylikorkala et al 1981) and in placenta (Walsh 1985).…”