Effects of β-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

Abstract

Recent studies have reported that β-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether β-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the β-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 μg∙kg−1 min−1; (b) Isop at a dose of 0.08 μg∙kg−1∙min−1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 μg∙kg−1∙min−1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2α or 13,14-dihydro-15-keto-PGF2α (PGFM)) concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 μg∙kg−1∙min−1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2α or PGFM) concentrations. No changes in plasma PGE2, PGF2α, or PGFM occurred during saline infusion. The data suggest that β-adrenergic agonist infusion is associated with a differential increase in plasma PG levels in vivo, but that this effect is probably not related to the failure of Isop (0.16 μg∙kg−1∙min−1) to maintain inhibition of myometrial contractions.