The effects of indomethacin and prostaglandin E2 on the ethanol-induced suppression of ovine fetal breathing movements.
A study was performed to examine the role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of FBM, in which the objective was to test the hypothesis that fetal administration of PGE2 can suppress the incidence of FBM following reversal of ethanol-induced suppression of FBM by indomethacin, a fatty acid cyclooxygenase inhibitor. Instrumented near-term pregnant ewes received 1-h maternal infusion of ethanol (1 g/kg maternal body weight) followed 0.5 h later by a 3-h fetal infusion of indomethacin (1 mg/kg fetal body weight/h), and then a 2-h fetal infusion of PGE2 (400 ng/kg fetal body weight/min). Prior to drug administration, FBM occurred approximately 36.1 +/- 2.6% of the time. FBM were suppressed during the period of ethanol infusion (9.6 +/- 1.7%); the ethanol-induced suppression of FBM was reversed by fetal indomethacin treatment (77.5 +/- 14.1%); shortly after the onset of fetal PGE2 infusion, the incidence of FBM decreased to a 2-h mean incidence of 14.1 +/- 4.2%, which was similar in magnitude to that observed after maternal ethanol infusion. After the completion of PGE2 infusion, the incidence of FBM rapidly increased to a peak incidence of 83.4 +/- 19.2%, which was indicative of a prolonged effect of indomethacin on FBM. The data indicate that PGs mediate the ethanol-induced suppression of ovine FBM and that the action of indomethacin to antagonize ethanol-induced suppression of FBM is primarily due to its inhibition of PG synthesis.
Smith
G N
GN
Department of Physiology, Lawson Research Institute, University of Western Ontario, London, Canada.
Sinervo
K R
KR
Carmichael
L
L
Patrick
J
J
Bocking
A D
AD
Brien
J F
JF
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology*; D004336:Drug Antagonism; D000431:Ethanol; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012119:Respiration / Q000187:drug effects*; D012756:Sheep; D013997:Time Factors
D000431:Ethanol; D015232:Dinoprostone; D007213:Indomethacin