Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003907:Dexamethasone; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004576:Electromyography; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005938:Glucocorticoids; D009280:Naphthaleneacetic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy; D011453:Prostaglandins / Q000097:blood*; D012756:Sheep; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D014599:Uterus / Q000502:physiology