Anti-hypertensive therapy and the feto-placental circulation: effects on umbilical artery resistance

J Perinat Med. 2004;32(4):315-9. doi: 10.1515/JPM.2004.058.

Abstract

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)).

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Fetus / blood supply*
  • Humans
  • Hydralazine / administration & dosage
  • Hydralazine / pharmacology
  • Hydralazine / therapeutic use
  • Labetalol / administration & dosage
  • Labetalol / pharmacology
  • Labetalol / therapeutic use
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacology
  • Magnesium Sulfate / therapeutic use
  • Methyldopa / administration & dosage
  • Methyldopa / pharmacology
  • Methyldopa / therapeutic use
  • Nifedipine / administration & dosage
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Placenta / blood supply*
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Regional Blood Flow
  • Umbilical Arteries / drug effects
  • Umbilical Arteries / physiology*
  • Vascular Resistance / drug effects

Substances

  • Antihypertensive Agents
  • Hydralazine
  • Methyldopa
  • Magnesium Sulfate
  • Nifedipine
  • Labetalol