PROSTACYCLIN SYNTHESIS IN OVINE PULMONARY-ARTERY IS DEVELOPMENTALLY-REGULATED BY CHANGES IN CYCLOOXYGENASE-1 GENE-EXPRESSION
PROSTACYCLIN SYNTHESIS IN OVINE PULMONARY-ARTERY IS DEVELOPMENTALLY-REGULATED BY CHANGES IN CYCLOOXYGENASE-1 GENE-EXPRESSION
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DOI：
10.1172/jci117220
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发表时间：
1994-05-01
影响因子：
15.9
通讯作者：
SHAUL, PW
中科院分区：
文献类型：
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作者：
BRANNON, TS;NORTH, AJ;SHAUL, PW
前列环素（PGI(2)）是妊娠晚期和新生儿肺血管舒缩性张力的关键介质，其在全肺中的产生在此期间增加。我们研究了妊娠110 ~ 115 d （F1）和125 ~ 135 d胎羔羊（F2，足月= 144 d）以及1和4周龄新生羔羊（NB1和NB2）肺内动脉（PA）段PGI(2)合成的发育调控。基础PGI(2)从Fl到F2增加4倍，从F2到NB1增加4倍，从NB1到NB2增加2倍。在所有年龄组中，66-72%的PGI(2)来源于内皮细胞。PGI(2)随着完整和剥离内皮节段的成熟而增加。在来自F2、NB1和NB2的完整PA中，基底PGI(2)的合成和合成在缓激肽、A23187或花生四烯酸的刺激下最大程度地随着发育而上升。相比之下，外源性环加氧酶产物PGH(2)刺激的PGI(2)合成在所有年龄段都是相似的。免疫印迹分析F2， NB1和NB2的PA显示环氧化酶-1蛋白的成熟增加了六倍；环氧化酶-2异构体未检出。全肺环氧化酶-1 mRNA丰度也随发育而升高。因此，绵羊PA内皮和血管平滑肌中PGI(2)的合成在胎儿晚期和新生儿早期显著增加；这种增加是由于环加氧酶活性的增加与环加氧酶-1的表达增强有关。我们得出结论，PA环加氧酶-1基因表达存在发育调控，这可能对新生儿成功的心肺过渡和功能至关重要。
Prostacyclin (PGI(2)) is a key mediator of pulmonary vasomotor tone during late gestation and in the newborn, and its production in whole lung increases during that period. We investigated the developmental regulation of PGI(2) synthesis in ovine intrapulmonary artery (PA) segments from 110 to 115 d (F1) and 125 to 135 d gestation fetal lambs (F2, term = 144 d) and 1- and 4-wk-old newborn lambs (NB1 and NB2). Basal PGI(2) rose fourfold from Fl to F2, fourfold from F2 to NB1, and twofold from NB1 to NB2. In all age groups 66-72% of PGI(2) was derived from the endothelium. Similar fold increases in PGI(2) were observed with maturation in intact and endothelium-denuded segments. In intact PA from F2, NB1, and NB2, basal PGI(2) synthesis and synthesis maximally stimulated by bradykinin, A23187, or arachidonic acid rose with development in a comparable manner. In contrast, PGI(2) synthesis stimulated by exogenous PGH(2), the product of cyclooxygenase, was similar at all ages. Immunoblot analyses of PA from F2, NB1, and NB2 revealed that there is a sixfold maturational increase in cyclooxygenase-1 protein; the cyclooxygenase-2 isoform was not detectable. Cyclooxygenase-1 mRNA abundance in whole lung also rose with development. Thus, PGI(2) synthesis in ovine PA endothelium and vascular smooth muscle increases markedly during late fetal and early newborn life; the increase is due to a rise in cyclooxygenase activity related to enhanced expression of cyclooxygenase-1. We conclude that there is developmental regulation of PA cyclooxygenase-1 gene expression, and that this may be critical to successful cardiopulmonary transition and function in the newborn.