Anti-hypertensive therapy and the feto-placental circulation: effects on umbilical artery resistance.
OBJECTIVE
To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro.


METHODS
Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alpha-methyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as -logEC50 (pD2) and mean maximal inhibition values for each compound.


RESULTS
All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alpha-methyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89+/-7.99%] versus all other agents [range 63.15+/-8.70-84.12+/-3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater PD2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (PD2 value [5.82+/-0.34] versus the above groups [range 3.10+/-0.09-3.52+/-0.14] (P <0.01)).


CONCLUSIONS
These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alpha-methyldopa, have significant direct effects on the feto-placental circulation. These results suggest that alpha-methyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.
Houlihan
Diarmaid D
DD
Department of Obstetrics and Gynecology, Clinical Sciences Institute, National University of Ireland Galway, University College Hospital, Galway, Ireland. john.morrison@nuigalway.ie
Dennedy
Michael C
MC
Ravikumar
Nandini
N
Morrison
John J
JJ
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007741:Labetalol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008750:Methyldopa / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010920:Placenta / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000503:physiopathology*; D011247:Pregnancy; D012039:Regional Blood Flow; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D006830:Hydralazine; D008750:Methyldopa; D008278:Magnesium Sulfate; D009543:Nifedipine; D007741:Labetalol