The relaxant effect of nifedipine in human uterine smooth muscle and the BK(Ca) channel

Am J Obstet Gynecol. 2008 Feb;198(2):237.e1-8. doi: 10.1016/j.ajog.2007.08.074.

Abstract

Objective: The purpose of this study was to investigate the effects of K+ channel blockade on the uterorelaxant effects of nifedipine in human myometrium during pregnancy.

Study design: Biopsies of human myometrium were obtained at elective cesarean section (n = 24). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were subjected to K+ channel blockade using tetraethylammonium (TEA) or iberiotoxin (IbTX) followed by cumulative additions of nifedipine (1 nmol/L-10 micromol/L). Control experiments were run simultaneously. Integrals of contractile activity were measured using the PowerLab hardware unit and Chart v3.6 software. Data were analyzed using one-way analysis of variance (ANOVA) followed by post hoc analysis.

Results: Nifedipine exerted a potent and cumulative inhibitory effect on spontaneous contractions and oxytocin-induced contractions in human myometrium in vitro, in comparison to control measurements (P < .05, n = 6). Incubation of strips with TEA or IbTX, prior to addition of nifedipine, significantly attenuated the relaxant effect exerted by nifedipine (P < .05, n = 6).

Conclusion: This study demonstrates that the uterorelaxant effect of nifedipine is attenuated by potassium channel (K+) blockade. This suggests that K+ channel conductance, and particularly the BK(Ca) channel, plays a role in the potent relaxant effect of nifedipine, hitherto presumed to act solely through L-gated calcium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Nifedipine / administration & dosage
  • Nifedipine / pharmacology*
  • Nifedipine / therapeutic use
  • Obstetric Labor, Premature / prevention & control
  • Potassium Channels, Calcium-Activated / drug effects*
  • Potassium Channels, Calcium-Activated / metabolism
  • Pregnancy
  • Tocolytic Agents / administration & dosage
  • Tocolytic Agents / pharmacology*
  • Tocolytic Agents / therapeutic use
  • Uterine Contraction / drug effects
  • Uterus / drug effects*
  • Uterus / metabolism

Substances

  • Calcium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Tocolytic Agents
  • Nifedipine