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Original Article

Effects of Labetalol on the Releas of Prostacyclin and Endothelin-1 by Cultured Human Umbilical Vein Endothelial Cells and on the Excretion of Prostacyclin and Thromboxane Metabolites in Preeclamptic Patients

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Pages 361-369 | Published online: 07 Jul 2009
 

Abstract

Objective: Labetalol reduces blood pressure primarily by blocking alpha-and beta-receptors, but other mechanisms of action may also be possible. We studied the effects of labetalol on the synthesis of vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin-1 (ET-1) by cultured human umbilical vein endothelial cells (HUVECs). We also studied the effect of oral labetalol treatment on PGI, and thromboxane A2 (TxA.2) production in preeclamptic patients.

Methods: HUVECs were incubated in the absence (control) and presence of labetalol (10−8-10-5 mol/L) and the release of PGI-, as measured by its metabolite 6-keto-PGF, and that of ET-1, were assessed by radioimmuno- assays. Because the presence of serum strongly affects endothelial cell function, we studied the effect of labetalol in HUVECs incubated with or without serum. In the in vivo part of the study, urine samples collected before and during oral labetalol intake were assessed for 2,3-dinor-6-keto-PGF, a metab-olite of PGI.1α and for 2,3-dinor-thromboxane-B., a metabolite of TxA,2 with high-pressure liquid chromatography and radioimmunoassay.

Results: HUVECs incubated in the presence of serum (10%) produced 8 times more 6-keto-PGFloi and 5 times more ET-1 than HUVECs incubated without serum. Labetalol (10−8-10−5 mol/L) did not affect the production of PGL, although the highest labetalol level (not achievable in vivo, 10−5 mol/L) was accompanied by a drop in PG1-, release in both serum-free (– 21%) and serum conditions (- 14%); this was probably a sign of toxic effect. Labetalol caused no consistent change in the release of ET-1 in HUVECs. Oral labetalol treatment did not affect urinary excretion of PGI, and TxA., metabolites.

Conclusions: No clinically relevant effects of labetalol were found on endothelial cell PG1-, or ET-1 production. Labetalol at therapeutic doses and concentrations does not affect the production of vasoactive PGI2 and TxA2 in preeclamptic patients.

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