15-keto-13-14-dihydroprostaglandin-f2alpha and 6-methoxy-2-naphthylacetic-acid

The purpose of the study was to determine the effects of selective prostaglandin synthase type 2 inhibitors on basal prostaglandin concentrations in the fetal and maternal circulations and on the labor-associated increase in prostaglandin production in sheep.. The effects of maternal nimesulide (0.01, 0.1, and 1 mg/kg) and 6-methoxy-2-naphthylacetic acid (1, 5, and 10 mg/kg) administration were examined (n = 5) at 134 +/- 1 days' gestation. At 138 days' gestation premature labor was induced by fetal dexamethasone infusion (1 mg/d). Ewes were treated with either vehicle or nimesulide infusion (20 mg. d-1. kg-1, n = 5 per group).. Nimesulide and 6-methoxy-2-naphthylacetic acid decreased basal prostaglandin production in a concentration-dependent manner. Delivery of nimesulide-treated ewes was delayed by >/=17 hours with respect to that of control ewes (53.9 +/- 2.6 hours). In 2 nimesulide-treated ewes labor did not progress to delivery despite membrane rupture. The increase in prostaglandin concentrations usually seen during dexamethasone-induced labor was abolished in nimesulide-treated ewes and also in their fetuses.. Highly selective inhibitors of prostaglandin endoperoxidase H synthase 2 may be required to spare fetal prostaglandin production and limit potential side effects during the suppression of preterm labor.

Topics: Animals; Cyclooxygenase Inhibitors; Dexamethasone; Dinoprost; Dinoprostone; Electromyography; Female; Fetal Blood; Glucocorticoids; Naphthaleneacetic Acids; Obstetric Labor, Premature; Pregnancy; Prostaglandins; Sheep; Sulfonamides; Uterus