Hydrogen peroxide and superoxide anion modulate pregnant human myometrial contractility.
Reactive oxygen species (ROS) have the propensity to cause macromolecular damage with consequent modification of cellular function. We investigated the effects of two particular oxidants, superoxide (O2(-)) anions and hydrogen peroxide (H2O2), on oxytocin-induced myometrial contractility using biopsies from women undergoing Caesarean section at term gestation. Isometric tension recordings were performed and concentration-response curves derived after addition of test agents. A maximal reduction in myometrial contractility to 27.2 +/- 4.5% of control was observed followed application of H2O2. The enzyme scavenger catalase (CAT) reduced the inhibitory effect of H2O2 but had little effect at 10-fold lower concentrations. Addition of dialysed xanthine oxidase +/- hypoxanthine significantly inhibited contractility to 23.8.0 +/- 4.2% compared with control. Pre-incubation with superoxide dismutase and CAT diminished this effect. The non-specific potassium channel blocker, tetraethylammonium chloride (1 mM), had no effect on myometrial contractility. We conclude that human myometrium is susceptible to the effects of ROS, which may be produced by reperfusion-ischaemic episodes during labour. Our findings could, in part, explain the weak or prolonged depression of contractions characteristic of myometrial dysfunction culminating in difficult labours.
Warren
Averil Y
AY
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, The Medical School, Derby DE22 3DT, UK.
Matharoo-Ball
Balwir
B
Shaw
Robert W
RW
Khan
Raheela N
RN
D000838:Anions; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D013481:Superoxides / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000838:Anions; D010120:Oxytocics; D013481:Superoxides; D010121:Oxytocin; D006861:Hydrogen Peroxide