The effects of dihydralazine, labetalol and magnesium sulphate on the isolated, perfused human placental cotyledon.
OBJECTIVE
To assess the effects of dihydralazine, labetalol and magnesium sulphate on the vascular tone in the isolated, perfused human placental cotyledon.


METHODS
In vitro perfusion of the fetal compartment of isolated, human placental cotyledons.


RESULTS
None of the drugs affected basal vascular tone. The thromboxane A2-mimic U46619 and endothelin-1 induced a concentration-dependent increment in perfusion pressure, while 5-hydroxytryptamine induced a variable increase, and norepinephrine induced a small, transient increase in perfusion pressure. After preconstriction with U46619, magnesium sulphate (1.5 x 10(-3) to 6 x 10(-3) mol/l) induced a decrease in perfusion pressure, while dihydralazine (10(-6) to 10(-4) mol/l) or labetalol (10(-7) to 10(-4) mol/l) enhanced the perfusion pressure. These effects of dihydralazine and labetalol were unaffected by treatment with indomethacin 10(-6) mol/l, but could be reversed by addition of magnesium sulphate 6 x 10(-3) mol/l. Labetalol 10(-6) to 10(-4) mol/l also caused an increase in the perfusion pressure induced by endothelin-1, but showed no effects after preconstriction with 5-hydroxytryptamine. Pretreatment with labetalol 10(-4) mol/l inhibited the transient increase in perfusion pressure induced by norepinephrine 3 x 10(-5) mol/l.


CONCLUSIONS
The present data demonstrated that the commonly used vasodilating agents labetalol and dihydralazine do not produce vasodilatation in the human perfused cotyledon after vasoconstriction induced by agents of suggested importance for maintenance of fetal placental vascular tone, and that high concentrations of these drugs may even enhance vasoconstriction induced by thromboxane and endothelin-1 in this area. Magnesium sulphate may show the potential to reverse such unwanted effects of dihydralazine and labetalol.
Petersen
O B
OB
Department of Obstetrics and Gynaecology, Aarhus University Hospital, Denmark.
Skajaa
K
K
Svane
D
D
Gregersen
H
H
Forman
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004078:Dihydralazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D008278:Magnesium Sulfate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004078:Dihydralazine; D007741:Labetalol