The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F2 alpha in pregnant sheep.
OBJECTIVE
To determine whether ritodrine-stimulated production of prostaglandin (PG) F2 alpha by pregnant uterine tissues can be blocked by the concurrent administration of ketorolac, a PG synthesis inhibitor.


METHODS
We infused saline, ritodrine, ketorolac, or a combination of ritodrine and ketorolac into chronically catheterized pregnant sheep. Concentrations of PGF2 alpha in uterine venous plasma were measured by radioimmunoassay at 0, 1, 2, 3, 4, and 24 hours during the infusions.


RESULTS
Ritodrine significantly increased uterine venous PGF2 alpha; mean percent increases at 4 hours were 330% and 380%, and at 24 hours 370%, compared with controls. During concurrent ritodrine and ketorolac infusion, there was no increase in uterine venous PGF2 alpha at any time.


CONCLUSIONS
Ketorolac completely blocks ritodrine-stimulated production of PGF2 alpha in pregnant uterine tissues. We conclude that ritodrine stimulates PG production through mobilization of arachidonic acid, and this can be effectively blocked with a PG synthesis inhibitor. This finding may have important clinical applications in the treatment of preterm labor.
Rauk
P N
PN
Department of Obstetrics Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania.
Laifer
S A
SA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D020910:Ketorolac; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D012312:Ritodrine / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015237:Dinoprost; D014046:Tolmetin; D012312:Ritodrine; D020910:Ketorolac