Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep.
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)
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism; D011863:Radioimmunoassay; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D011453:Prostaglandins; D011460:Prostaglandins F; D015237:Dinoprost; D007545:Isoproterenol