Coceani F, Kelsey L
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1991 Feb;69(2):218-21. doi: 10.1139/y91-033.
Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight.min) both in the presence and absence of the endothelium. Anisomycin (10(-4) M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.
我们之前的研究表明，内皮素-1（ET-1）是动脉导管一种极为强效的收缩剂，且位于肌膜的细胞色素P-450系统对于血管对氧气的收缩反应至关重要。我们现在研究了近足月胎羊离体动脉导管制剂中ET-1的释放情况。无论有无内皮，制剂在基础条件下（约0.04 pg/100 mg湿重·分钟）均能产生可测量的ET-1量。茴香霉素（10⁻⁴ M）使这种释放减少了50%，而凝血酶（1 U/mL）使释放量增加了一倍。用一氧化碳混合物（CO/O₂ 比例为0.27）处理可抑制完整和去内皮制剂中ET-1的释放。我们提出，氧气通过引起特定细胞色素P-450的构象变化来触发出生时动脉导管的关闭，这反过来又为合成收缩剂ET-1提供信号。
