OBJECTIVE: To observe the effects of lysophosphatidic acid (LPA) on production of endothelin (ET) in rat aorta vascular smooth muscle cells (VSMCs). METHODS: Cultured VSMCs were used in the study. DNA synthesis of VSMCs was measured by 3H-TdR incorporation. The amount of ET mRNA of VSMCs was determined by competitive quantitative RT-PCR. The levels of synthesis and release of ET in VSMCs were determined by radioimmunoassay (RIA). RESULTS: 5-20 mumol.L-1 of LPA promoted VSMCs 3H-TdR incorporation in a concentration dependent manner. The amount of ET mRNA in VSMCs treated by 5-20 mumol.L-1 of LPA was increased by 16%, 21%, and 23%, respectively, compared with the control. After 8 hours of incubation, 5-20 mumol.L-1 of LPA elevated the ET production in a concentration dependent manner. After 8 hours of VSMCs incubated with LPA (5-20 mumol.L-1), the content of ET in medium was increased by 140%-200%, respectively, compared with the control. In addition, it was found that BQ123, a non-selective ET receptor antagonist, greatly decreased the VSMCs DNA synthesis induced by LPA. CONCLUSION: LPA stimulated the ET mRNA expression and ET production in VSMCs. The effects of LPA on VSMCs DNA synthesis were partly mediated by ET/ETA receptor pathway. It suggests that LPA and ET interact and exert biological effects as endogenous active peptides.
OBJECTIVE: To observe the effects of lysophosphatidic acid (LPA) on production of endothelin (ET) in rat aorta vascular smooth muscle cells (VSMCs). METHODS: Cultured VSMCs were used in the study. DNA synthesis of VSMCs was measured by 3H-TdR incorporation. The amount of ET mRNA of VSMCs was determined by competitive quantitative RT-PCR. The levels of synthesis and release of ET in VSMCs were determined by radioimmunoassay (RIA). RESULTS: 5-20 mumol.L-1 of LPA promoted VSMCs3H-TdR incorporation in a concentration dependent manner. The amount of ET mRNA in VSMCs treated by 5-20 mumol.L-1 of LPA was increased by 16%, 21%, and 23%, respectively, compared with the control. After 8 hours of incubation, 5-20 mumol.L-1 of LPA elevated the ET production in a concentration dependent manner. After 8 hours of VSMCs incubated with LPA (5-20 mumol.L-1), the content of ET in medium was increased by 140%-200%, respectively, compared with the control. In addition, it was found that BQ123, a non-selective ET receptor antagonist, greatly decreased the VSMCs DNA synthesis induced by LPA. CONCLUSION:LPA stimulated the ET mRNA expression and ET production in VSMCs. The effects of LPA on VSMCs DNA synthesis were partly mediated by ET/ETA receptor pathway. It suggests that LPA and ET interact and exert biological effects as endogenous active peptides.