Pathophysiological role of ET-1(1-31) on the inflammatory diseases.

1) ET- 1（1-31）作为炎症介质对人中性粒细胞和单核细胞表现出趋化活性。ET_A受体拮抗剂BQ123可以抑制ET-1（1-31）诱导的趋化作用，而ET_B受体拮抗剂BQ788则不能。2) ET-1（1-31）直接引起系膜细胞的迁移，并可能通过系膜细胞活化介导单核细胞的募集。由于人类cymase已被报道参与肾小球疾病，ET-1（1-31）可能是其中一种介质。3) ET-1（1-31）引起大鼠主动脉平滑肌细胞（RASMC） DMPO/OH自由基自旋加合物的电子顺磁共振信号显著增加。抗氧化剂通过抑制活性氧来抑制ET-1（1-31）诱导的RASMC增殖。抗氧化剂抑制细胞增殖的潜在机制可以部分解释为抑制JNK激活和由此产生的AP-1-DNA结合的抑制。4)腹主动脉瘤患者术前血浆ET-1（1-31）浓度高于健康人。手术后血浆ET-1（1-31）降至与健康受试者相似的水平。

1) ET- 1(1-31) exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mrdiator. The chemotactic effects induced by ET-1(1-31) was inhibited by BQ123, an ET_A receptor antagonist, but not by BQ788, an ET_B receptor antagonist.2) ET-1(1-31) directly cause the migration of mesangial cells and may be responsible for recruitment of mononuclear cells mediated through the mesangial cell activation. Since human cymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be one of the mediators.3) ET-1(1-31) caused a significant increase in the electron paramagnetic resonance signal of the DMPO/OH radical spin adduct in rat aortic smooth muscle cells(RASMC). Antioxidants inhibit ET-1(1-31)-induced RASMC proliferation by inhibiting reactive oxygen species. The underlying mechanisms of the inhibition of cellular proliferation by antioxidants may be explained, in part, by the inhibition of JNK activation and the resultant inhibition of AP-1-DNA binding.4) Before surgery in patients with abdominal aortic aneurysma, plasma concentrations of ET-1(1-31) were higher than those in healthy individuals. After surgery, ET-1(1-31) in plasma decreased to the levels similar to those of healthy subjects.