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内皮素（ｅｎｄｏｔｈｅｌｉｎ，ＥＴ）是已知的体内活性最强的缩血管物质，其缩血管作用由Ｇ蛋白偶联受体所介导。但ＥＴ强大的促血管平滑肌细胞（ＶＳＭＣ）增生效应的机理尚未完全阐明。本研究选用培养的兔胸主动脉ＶＳＭＣ，探讨丝裂素活化蛋白激酶（ＭＡＰＫ）在ＥＴ促细胞增生中的作用。结果表明：ＥＴ－１呈时间和浓度依赖性地促进细胞摄取￣３Ｈ－ＴｄＲ和激活ＭＡＰＫ，此作用可被蛋白激酶Ｃ（ｐｒｏｔｅｉｎｋｉｎａｓｅＣ，ＰＫＣ）抑制剂Ｓｔａｕｒｏｓｐｏｒｉｎｅ（ＳＴＰ），Ｈ－７和ＥＴ＿Ａ受体拮抗剂ＢＱ１２３所抑制，但不被酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ（Ｈｅｒｂ）所抑制，用ＰＫＣ激动剂ＰＭＡ（Ｐｈｏｒｂｏｌｍｙｒｉｓｔａｔｅａｃｅｔａｔｅ）预处理ＶＳＭＣ，使其ＰＫＣ活性下调，可显著减弱ＥＴ－１对ＭＡＰＫ的激活能力。本结果提示：（１）ＭＡＰＫ参与ＥＴ－１所致的ＶＳＭＣ增生；（２）ＥＴ－１促细胞增生与激活ＭＡＰＫ的作用是由ＥＴ＿Ａ受体和ＰＫＣ介导的。
Endothelin (ET) is the most active vasoconstrictor known in the body and its vasoconstrictive effect is mediated by G-protein coupled receptors. However, the mechanism by which ET has a strong proliferative effect on vascular smooth muscle cells (VSMCs) has not yet been fully elucidated. In this study, cultured rabbit aortic VSMCs were used to investigate the role of mitogen-activated protein kinase (MAPK) in ET-induced cell proliferation. The results showed that ET-1 promoted the cellular uptake of 3H-TdR and activated MAPK in a time and concentration-dependent manner. This effect could be inhibited by Staurosporine (STP), H-7 and ET-A receptors of protein kinase C (PKC) Antagonist BQ123, but not by the tyrosine kinase inhibitor Herbimycin A (Herb). Pretreatment of VSMC with PKC agonist PMA (Phorbolmyristate acetate) reduced its PKC activity and significantly attenuated the activation of MAPK by ET-1 ability. The results suggest that: (1) MAPK is involved in the proliferation of VSMC induced by ET-1; (2) The effect of ET-1 on cell proliferation and activation of MAPK is mediated by ET-A receptor and PKC.