Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus

被引:42
作者
Clyman, RI
Hardy, P
Waleh, N
Chen, YQ
Maury, F
Fouron, JC
Chemtob, S
机构
[1] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[3] Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
关键词
prostaglandin E-2; prostaglandin I-2; 6-keto-prostaglandin F-1 alpha;
D O I
10.1152/ajpregu.1999.276.3.R913
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE(2) synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE(2) formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE(2) synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.
引用
收藏
页码:R913 / R921
页数:9
相关论文
共 40 条
[1]   SELECTIVE-INHIBITION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-1 (CYCLOOXYGENASE-1) BY VALERYLSALICYLIC ACID [J].
BHATTACHARYYA, DK ;
LECOMTE, M ;
DUNN, J ;
MORGANS, DJ ;
SMITH, WL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 317 (01) :19-24
[2]  
CHAN CC, 1995, J PHARMACOL EXP THER, V274, P1531
[3]   Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: The role of gestation, oxygen tension, and vasa vasorum [J].
Clyman, RI ;
Waleh, N ;
Black, SM ;
Riemer, RK ;
Mauray, F ;
Chen, YQ .
PEDIATRIC RESEARCH, 1998, 43 (05) :633-644
[4]   Changes in endothelial cell and smooth muscle cell integrin expression during closure of the ductus arteriosus: An immunohistochemical comparison of the fetal, preterm newborn, and full-term newborn rhesus monkey ductus [J].
Clyman, RI ;
Goetzman, BW ;
Chen, YQ ;
Mauray, F ;
Kramer, RH ;
Pytela, R ;
Schnapp, LM .
PEDIATRIC RESEARCH, 1996, 40 (02) :198-208
[5]   PGE2 IS A MORE POTENT VASODILATOR OF LAMB DUCTUS-ARTERIOSUS THAN IS EITHER PGI2 OR 6-KETO PGF1-ALPHA [J].
CLYMAN, RI ;
MAURAY, F ;
ROMAN, C ;
RUDOLPH, AM .
PROSTAGLANDINS, 1978, 16 (02) :259-264
[6]  
CLYMAN RI, 1989, CIRC RES, V64, P1
[7]  
CLYMAN RI, 1978, BIOL NEONATE, V34, P177
[8]   INVOLVEMENT OF INTRAMURAL PROSTAGLANDIN-E2 IN PRENATAL PATENCY OF THE LAMB DUCTUS-ARTERIOSUS [J].
COCEANI, F ;
HUHTANEN, D ;
HAMILTON, NC ;
BISHAI, I ;
OLLEY, PM .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1986, 64 (06) :737-744
[9]   PROSTAGLANDIN-I2 IS LESS RELAXANT THAN PROSTAGLANDIN-E2 ON LAMB DUCTUS-ARTERIOSUS [J].
COCEANI, F ;
BODACH, E ;
WHITE, E ;
BISHAI, I ;
OLLEY, PM .
PROSTAGLANDINS, 1978, 15 (04) :551-556
[10]   RESPONSE OF DUCTUS-ARTERIOSUS TO PROSTAGLANDINS [J].
COCEANI, F ;
OLLEY, PM .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1973, 51 (03) :220-225