The combined uterorelaxant effect of sildenafil and terbutalin in the rat: The potential benefit of co-administration of low doses

Abstract

Aims: Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with β2-mimetic terbutaline in an isolated organ bath and to perform in vivo smooth muscle electromyographic studies in pregnant rats. The modifications in uterine cAMP/cGMP levels were also detected. Main methods: Contractions of non-pregnant and 5/15/18/20/22-day pregnant uterine rings were measured in an isolated organ bath system in the presence of sildenafil alone or with terbutaline. The uterine levels of cAMP and cGMP were determined by commercial ELISA assays. The in vivo efficacy of the combination was measured by smooth muscle electromyography. Key findings: Sildenafil reduced uterine contractions in vitro and in vivo; additionally, terbutaline significantly increased the uterorelaxant effect of sildenafil in the lower concentration or dose ranges. Terbutaline enhanced the cGMP level increasing effect of sildenafil. Significance: The co-administration of sildenafil and terbutaline could be a promising tocolytic combination to reduce maternal and foetal adverse events and increase efficacy.

Keywords

• Uterine contractility
• β2-adrenoreceptor agonists
• Sildenafil citrate
• Tocolysis
• Pregnancy
• Preterm birth