The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F_2α in pregnant sheep

Objective: To determine whether ritodrine-stimulated production of prostaglandin (PG) F_2α 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 PGF_2α 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 PGF_2α; 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 PGF_2α at any time. Conclusions: Ketorolac completely blocks ritodrine-stimulated production of PGF_2α 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.