内皮素对离体大鼠主动脉及主动脉平滑肌细胞作用的研究

STUDIES ON EFFECT OF ENDOTHELIN ON RAT AORTA IN VITRO AND CULTURED AORTIC SMOOTH MUSCLE CELLS

本研究着重探讨内皮素对大鼠主动脉的收缩作用及对主动脉平滑肌细胞细胞周期及能量代谢的影响。浓度为1.0～18.0nmol/L的内皮素可引起大鼠主动脉产生浓度依赖性收缩,其EC_(50)为3.75±0.75nmol/L。正常对照组中平滑肌细胞S+G_2M期细胞的比例基本稳定在26.3％～29.6％的范围内;浓度为10.0和1000.0pmol/L的内皮素可使S+G_2M期细胞比例明显增高,上述变化呈良好的浓度依赖性(P<0.01);内皮素作用3～24h,随作用时间延长,S+G_2M期细胞比例逐步增多,呈明显的时间依赖性(P<0.01)。10.0pmol/L的内皮素作用10min后ATP含量增至对照组的139.05±1.11％(P<0.01);20min后ATP含量为对照组的65.25±5.09％(P<0.01),低于对照组水平。结果表明,内皮素具有缩血管作用及促平滑肌细胞增殖作用,上述作用可能在高血压的发病机制中有一定的意义。

Endothelin is one of the most potent vasoconstrictors known to date. The roles of endothelin in the pathogenesis of hypertensive diseases have attracted much attention since its discovery. In the present work, the effects of endothelin on the contractility of rat aorta in vitro, and the proliferation and ATP content of cultured vascular smooth muscle cells from rat aorta were studied.The results showed that endothelin could induce a dose-dependent contraction of rat aorta at concentrations of 1.0 to 18.0 nmol/ L and the EC50value was 3.75±0.75 nmol/ L. Under normal condition, the percentage of proliferative cells (S+G2M phase) of cultured vascular smooth muscle cells was 26.3%-29.6%. Endothelin had a dose-dependent (P<0.01) and time-dependent (P<0.01) proliferation-promotion effect on cultured vascular smooth muscle cells. 24 hours after exposure to endothelin, the percentages of proliferative cells increased to 40.7% and 45.6% at concentrations of 10.0 and 100.0 pmol/ L respectively. 10.0 pmol / L endothelin could induce a temporary increase (139.051 1.11%, P<0.01 ) in ATP content of cultured vascular smooth muscle cells as compared with the control group 10 min after addition of endothelin, but the ATP level dropped sharply to 65.25±5.09% (P<0.01 ) at 20 min and recovered slightly at 30 min (71.13±4.94%; P<0.01), suggesting that endothelin-induced responses of vascular smooth muscle cells are energy-consuming processes. These results suggest that the above effects of endothelin may play a certain role in the pathogenesis of hypertension.