Ritodrine increases leukotriene B4 concentrations in pregnant sheep.
OBJECTIVE
Our goals were (1) to determine if beta-adrenergic receptor stimulation leads to 5-lipoxygenase metabolism of arachidonic acid and (2) to determine if inhibition of prostaglandin synthase alters 5-lipoxygenase metabolism of arachidonic acid during beta-adrenergic stimulation.


METHODS
We infused saline solution, ritodrine (4 micrograms/kg/min), and a combination of ritodrine (4 micrograms/kg/min) and ketorolac (1.2 microgram/kg/min) into chronically catheterized pregnant sheep (gestational ages 110 to 120 days, term 147 days). With a radioimmunoassay we measured concentrations of leukotriene B4, a 5-lipoxygenase metabolite of arachidonic acid, in uterine venous and arterial plasma at 0, 2, and 4 hours during the infusion.


RESULTS
Both uterine venous and arterial leukotriene B4 were increased during ritodrine infusion (mean uterine venous increase at 2 hours 218%, p < 0.05; mean arterial increase at 2 hours 280%, p < 0.05). Concentrations during combined infusion of ritodrine and ketorolac increased significantly but were not different than concentrations observed during ritodrine infusion.


CONCLUSIONS
Infusion of the beta-agonist ritodrine leads to 5-lipoxygenase metabolism of arachidonic acid and increased concentrations of leukotriene B4. The increased concentration in both uterine venous and arterial plasma suggests a systemic source of leukotriene B4 production. Concurrent inhibition of prostaglandin synthase during ritodrine infusion does not change 5-lipoxygenase metabolism in this model.
Laifer
S A
SA
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine.
Rauk
P N
PN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001158:Arteries; D005260:Female; D007262:Infusions, Intravenous; D020910:Ketorolac; D007975:Leukotriene B4 / Q000097:blood*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood* / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012312:Ritodrine / Q000008:administration & dosage / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D012756:Sheep; D013997:Time Factors; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply; D014680:Veins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D007975:Leukotriene B4; D014046:Tolmetin; D012312:Ritodrine; D020910:Ketorolac