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Aim:To investigate the effects of tanshinone ⅡA(Tan ⅡA)on the regulation ofthe production of endothelin(ET)-1(including large ET-1),mRNA levels of ET-1,endothelin-converting enzyme-1(ECE-1),endothelin-A receptor(ET_A)andendothelin-B receptor(ET_B)induced by TNF-α in rat brain microvascular endo-thelial cells(BMVEC).Methods:The ET-1 release(including large ET-1)into theculture medium was determined by enzyme immunoassay.The levels of ET-1,ECE- 1,ET_A,and ET_B mRNA were measured by RT-PCR.Endothelin receptor bind-ing was also tested.Results:The induction of ET-1 release by TNF-α from cul-tured BMVEC was dose-dependently reduced by Tan IIA,but large ET-1 levelsprogressively increased in response to Tan ⅡA;the mRNA expression of ET-1 wasunaffected.Tan ⅡA also caused a decrease in ET_A receptor mRNA and ECE-1expression in a dose-dependent manner.Endothelin receptor binding was unal-tered in BMVEC stimulated with TNF-α alone or a combination of TNF-α and TanⅡA.Conclusion:These findings suggest that Tan ⅡA may inhibit ET-1 produc-tion in TNF-α-induced BMVEC through the suppression of ECE-1 synthesis.
Aim: To investigate the effects of tanshinone IIA (Tan IIA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1, endothelin-converting enzyme-1 (ECE-1) ),endothelin-A receptor(ET_A)andendothelin-B receptor(ET_B)induced by TNF-α in rat brain microvascular endo-thelial cells(BMVEC).Methods:The ET-1 release(including large ET-1)into the culture medium Was determined by enzyme immunoassay.The levels of ET-1,ECE-1,ET_A,and ET_B mRNA were measured by RT-PCR.Endothelin receptor bind-ing was also tested.Results:The induction of ET-1 release by TNF- α from cul-tured BMVEC was dose-dependently reduced by Tan IIA,but large ET-1 levelsprogressively increased in response to Tan IIA;the mRNA expression of ET-1 wasunaffected.Tan IIA also caused a decrease in ET_A receptor mRNA and ECE- 1expression in a dose-dependent manner.Endothelin receptor binding was unal-tered in BMVEC stimulated with TNF-α alone or a combination of TNF-α and TanIIA.Conclusion:These Conclusion suggest that Tan IIA may inhibit ET-1 produc-tion in TNF-α-induced BMVEC through the suppression of ECE-1 synthesis.