ATP-sensitive potassium channels modulate in vitro tocolytic effects of β2-adrenergic receptor agonists on uterine muscle rings in rats in early but not in late pregnancy

Abstract

Aim: To investigate whether ATP-sensitive potassium (KATP) channels modulate the tocolytic effect of β2-adrenergic receptor (β2-AR) agonists (ritodrine and salmeterol) in early- pregnant (day 6) and late-pregnant (day 22) rat uterus in vitro, in order to examine the relation between the KATP channel sulphonylurea-binding regulatory subunit (SUR) expression and pharmacological reactivity of β2-AR agonists. Methods: The tocolytic effects of ritodrine and salmeterol (10-10-10-5 M) on spontaneous rhythmic contractions were investigated cumulatively, alone, or in the presence of the KATP channel blocker glibenclamide (10-6 M) and the KATP channel opener pinacidil (10-9-10-7 M) after 5-min preincubation. Results: β2-AR agonist induced myometrial relaxation was inhibited by glibenclamide and enhanced by pinacidil on day 6, when SUR1 expression levels were high. Neither glibenclamide nor pinacidil mediated tocolytic effect was measured on day 22. Conclusion: Low expression of the KATP channels at the end of gestation may facilitate enhanced excitability and contractility in the rat myometrium. The combination of a betamimetic and a KATP channel opener will therefore not be of therapeutic relevance in the treatment of preterm delivery.