Constriction of the ductus arteriosus by selective inhibition of cyclooxygenase-1 and -2 in near-term and preterm fetal rats

Prostaglandins & Other Lipid Mediators
Katsuaki ToyoshimaKazuo Momma

Abstract

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.

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Citations

Jun 17, 2010·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Utako YokoyamaYoshihiro Ishikawa
Jul 31, 2009·Journal of Perinatology : Official Journal of the California Perinatal Association·P ZielinskyL Almeida
Nov 5, 2011·Journal of Perinatology : Official Journal of the California Perinatal Association·P ZielinskyS C Garcia
Mar 12, 2015·Journal of Neonatal-perinatal Medicine·F GenoveseM A Palumbo
Oct 28, 2016·Circulation Journal : Official Journal of the Japanese Circulation Society·Shujiro FujitaYoshihiro Ishikawa
Oct 14, 2018·Transfusion·Manon GijtenbeekMonique C Haak
May 20, 2018·The Journal of Pharmacology and Experimental Therapeutics·Oliver PohlJean-Pierre Gotteland
Dec 18, 2013·Birth Defects Research. Part C, Embryo Today : Reviews·Paulo Zielinsky, Stefano Busato
Aug 9, 2016·Drug and Chemical Toxicology·Marla HahnSolange Cristina Garcia
Sep 5, 2014·American Journal of Physiology. Renal Physiology·A L KentJ E Dahlstrom
May 13, 2021·Scientific Reports·Paulo ZielinskyIzabele Vian

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