Lüscher T F, Yang Z, Tschudi M, von Segesser L, Stulz P, Boulanger C, Siebenmann R, Turina M, Bühler F R
Department of Research, University Hospital, Basel, Switzerland.
Circ Res. 1990 Apr;66(4):1088-94. doi: 10.1161/01.res.66.4.1088.
Endothelin-1 is a 21-amino acid endothelial vasoconstrictor peptide that may be the physiological antagonist of endothelium-derived relaxing factor (EDRF). Endothelin-1 (10(-11)-3 x 10(-7) M) evoked potent contractions of isolated internal mammary arteries, internal mammary veins, and saphenous veins, which were enhanced in internal mammary veins as compared with internal mammary arteries (concentration shift, 6.3-fold; p less than 0.05) but not in the saphenous veins. Endothelial removal augmented the response to the peptide (at 3 x 10(-7) M) in internal mammary arteries (p less than 0.05) but not in veins. In the artery, EDRF released by acetylcholine or bradykinin reversed endothelin-1-induced contractions; in saphenous veins, both agonists were much less effective compared with the artery and veins contracted with norepinephrine (p less than 0.005-0.01). This inhibition of endothelium-dependent relaxations in veins occurred at half-maximal contractions but was most prominent at maximal contractions to the peptide. Nitric oxide similarly inhibited contractions to endothelin-1 and norepinephrine in internal mammary arteries, whereas in veins that were contracted with endothelin-1 but not with norepinephrine, the relaxations were blunted (p less than 0.005). The nitric oxide donor SIN-1 and sodium nitroprusside induced complete relaxations of internal mammary arteries but were less effective in veins contracted with endothelin-1 (p less than 0.005). Thus, in normal human arteries, EDRF inhibits endothelin-1-induced contractions, whereas the peptide specifically attenuates the effects of EDRF and nitrovasodilators in veins. This may be important in pathological conditions associated with increased levels of endothelin-1 and in veins used as coronary bypass grafts.
内皮素-1是一种由21个氨基酸组成的内皮血管收缩肽，可能是内皮源性舒张因子（EDRF）的生理拮抗剂。内皮素-1（10^(-11)-3×10^(-7)M）可引起离体乳内动脉、乳内静脉和大隐静脉的强烈收缩，与乳内动脉相比，乳内静脉的收缩增强（浓度偏移6.3倍；p<0.05），而大隐静脉则无此现象。去除内皮可增强乳内动脉对该肽（3×10^(-7)M）的反应（p<0.05），但对静脉无此作用。在动脉中，乙酰胆碱或缓激肽释放的EDRF可逆转内皮素-1引起的收缩；在大隐静脉中，与动脉相比，这两种激动剂的作用均弱得多，且静脉与去甲肾上腺素收缩（p<0.005-0.01）。静脉中内皮依赖性舒张的这种抑制发生在半数最大收缩时，但在对该肽的最大收缩时最为明显。一氧化氮同样抑制乳内动脉对内皮素-1和去甲肾上腺素的收缩，而在与内皮素-1收缩但不与去甲肾上腺素收缩的静脉中，舒张作用减弱（p<0.005）。一氧化氮供体SIN-1和硝普钠可使乳内动脉完全舒张，但对与内皮素-1收缩的静脉作用较弱（p<0.005）。因此，在正常人动脉中，EDRF抑制内皮素-1引起的收缩，而该肽则特异性减弱EDRF和硝基血管扩张剂在静脉中的作用。这在与内皮素-1水平升高相关的病理状态以及用作冠状动脉旁路移植的静脉中可能具有重要意义。
