DRUG ANTAGONISM OF TNF INDUCED PROLIFERATION OF BOVINE CEREBROMICROVASCULAR SMOOTH MUSCLE CELLS

Effects of tumor necrosis factor(TNF ) on the proliferation of bovine cerebromic-rovascular smooth muscle cells(BCSMC) were investigated.At concentrations from 5 0 to 5 0 0 0U· mL^-1, TNF was shown to induce proliferation of cultured BCSMC in a dose-dependent manner. After 24 h incubation of the cells,TNF significantly stimulated the proliferation of BCSMC andreached maximal effects after 48 h incubation , then the effects slightly decreased.At concentrations from l0^-6 to l0^-4mol·L^-1,both imperatorin ( Imp) and iso-imperatorin(Isi)were found to antagonize the TNF induced proliferation of BCSMC. Their maximal inhibitoryeffects were 42. 2 and 36.1%at l0^-4 mol·L^-1 respectively.6-(α,α-diphenylacetylpiperazinly)pheny1-5- methyl-4,5- dihydro-3(2H)-pyridazinone(DMDP ) and 6-(α-phenylacetylpiperazinyl)phenyl- 5- methy-4,5-dihydro-3(2H)- pyridazinone (PMDP) were also found to possess similar effectat lower concentration(10^-6mol·L^-1),but no significant effect was observed when the drugconcentration was higher.