Maguire J J, Davenport A P
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital.
Br J Pharmacol. 1998 Sep;125(2):238-40. doi: 10.1038/sj.bjp.0702102.
Overproduction of the potent vasoconstrictor peptide endothelin-1 (ET-1) is implicated in the pathogenesis of coronary artery disease. In endothelium-denuded human coronary arteries the response to big ET-1 was significantly enhanced in atherosclerotic arteries (coronary artery disease, CAD; n=7) with an EC50 value of 96 nM (57- 161 nM, 95% C.I.) compared to 274 nM (205-365 nM) in non-diseased arteries (dilated cardiomyopathy, DCM; n=10) (Mann-Whitney U-test, P<0.05). Higher levels of immunoreactive endothelin (ET) could be detected by radioimmunoassay in bathing medium taken from CAD arteries than from DCM arteries (2.8+/-0.5 nM, n=5 vs 1.1+/-0.2 nM, n=7) (Student's two-tailed t-test, P<0.05). There were no differences in responses of arteries from either group to ET-1 (EC50 10 nM, CAD vs 14 nM, DCM). The enhanced response of atherosclerotic human coronary arteries to big ET-1 appears to be due to up-regulation of endothelin-converting enzyme (ECE) activity rather than to an augmented response of the arteries to ET-1. This non-endothelial ECE may therefore be an important therapeutic target in coronary artery disease.
强效血管收缩肽内皮素-1（ET-1）的过度产生与冠状动脉疾病的发病机制有关。在去内皮的人冠状动脉中，与非病变动脉（扩张型心肌病，DCM；n = 10）相比，动脉粥样硬化动脉（冠状动脉疾病，CAD；n = 7）对大ET-1的反应显著增强，EC50值为96 nM（57 - 161 nM，95%置信区间），而非病变动脉的EC50值为274 nM（205 - 365 nM）（曼-惠特尼U检验，P < 0.05）。通过放射免疫测定法可检测到，从CAD动脉采集的浴液培养基中免疫反应性内皮素（ET）水平高于DCM动脉（2.8±0.5 nM，n = 5 对比 1.1±0.2 nM，n = 7）（学生双尾t检验，P < 0.05）。两组动脉对ET-1的反应无差异（EC50，CAD为10 nM，DCM为14 nM）。动脉粥样硬化的人冠状动脉对大ET-1反应增强似乎是由于内皮素转换酶（ECE）活性上调，而非动脉对ET-1的反应增强。因此，这种非内皮ECE可能是冠状动脉疾病的一个重要治疗靶点。
