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

Abstract

Recent studies have reported that beta-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 beta-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 beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.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 microgram.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 PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The Initiation and Inhibition of Labor - Toward a Molecular Understanding

“…In contrast, we found that de sensitization was associated with a significant re duction in the number (but not affinity) of β-adren ergic receptors. 41 We have observed similar examples of homolo gous myometrial desensitization to β-adrenergic agonists in vivo in rats 43 as well as nonpregnant 44 and pregnant sheep. 45 In the latter study preterm labor was induced in sheep by injection of the pro gesterone receptor antagonist, RU486.…”

“…22 Similarly, Casper and Lye found that intermittent administration of the short-acting β-adrenergic agonist isoproterenol pre vents the onset of myometrial desensitization in nonpregnant sheep. 44 Spalting and colleagues 52 have reported greater prolongation of pregnancy and in creased birth weights with intermittent pulses of fenoterol, as compared to continuous infusion. Other studies have suggested that agents other than betamimetics be used to initially arrest uterine contrac tions followed by a continuous basal infusion of terbutaline accompanied with intermittent boluses of this drug.…”