Constriction of the ductus arteriosus by selective inhibition of cyclooxygenase-1 and -2 in near-term and preterm fetal rats.
We studied the transplacental ductal constrictive effects of a selective cyclooxygenase (COX)-1 inhibitor (SC560), six selective COX-2 inhibitors including rofecoxib, and a non-selective COX inhibitor (indomethacin). Each drug was administered to the pregnant rats, and fetal ductus arteriosus (DA) was studied with a whole-body freezing method. The inner diameter ratio of the DA to the main pulmonary artery (DA/PA) was 1.02+/-0.03 (mean+/-S.E.M.) in controls. Every drug constricted the DA dose-dependently. In preterm rats on the 19th day of gestation, 10mg/kg of SC560, rofecoxib and indomethacin caused ductal constriction, with DA/PA reduced to 0.76+/-0.02, 0.80+/-0.03 and 0.75+/-0.02, respectively. In near-term on the 21st day, 10mg/kg of them caused ductal constriction, with DA/PA to 0.74+/-0.04, 0.26+/-0.02 and 0.33+/-0.05. In conclusion, both COX-1 and COX-2 selective inhibitors constrict fetal DA. They are not better alternatives for the fetus than non-selective COX inhibitors for tocolysis.
Toyoshima
Katsuaki
K
Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan. nqf37179@nifty.com
Takeda
Atsuhito
A
Imamura
Shinichiro
S
Nakanishi
Toshio
T
Momma
Kazuo
K
D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004374:Ductus Arteriosus, Patent / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D005333:Fetus / Q000002:abnormalities / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015145:Tocolysis / Q000009:adverse effects*; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2