Effect of nitric monoxide and carbon monoxide on bFGF stimulated proliferation of vascular smooth muscle cells

Objective: To investigate the effect of nitric oxide(NO) and carbon monoxide(CO) on proliferation of vascular smooth muscle cells(VSMC) stimulated by basic fibroblast growth factor(bFGF) and their mechanism. Methods: VSMC proliferation was measured by 3H TdR incorporation. Protein phosphorylation, PKC and MAPK activity in VSMC were determined by radioactivity assay. Results: Compared with control, VSMC amplification induced by bFGF was increased by 1.1 fold after 24 h incubation ( P 0.01). Protein phophorylation, PKC and MAPK activities in VSMC were augmented by 38.2%, 1.5 and 2.5 times, respectively ( P 0.01); H L Lys and L Arg had no significant influence on both growth and intracellular protein phosphorylation, PKC and MAPK activities in quiescent VSMC. 5, 10 and 20 μmol·L -1 H L Lys decreased bFGF stimulated VSMC proliferation by 43.4%,46.6% and47.6%,respectively ( P 0.01). Intracellular PKC activities were lowered by 25.6%, 31.8% and 33.9%, respectively ( P 0.01), and MAPK activities were reduced by 15.0%, 25.5% and 40.1%, respectively ( P 0.01); 5, 10 and 20 mmol·L -1 L Arg decreased bFGF stimulated VSMC proliferation by 30.2%, 40.5% and 51.9%, respectively ( P 0.01). Intracellular PKC activities were lowered by 29.8%, 28.9% and 36.6%,respectively ( P 0.01), and MAPK activities were reduced by 19.4%, 32.4% and 44.4%, respectively ( P 0.01). bFGF induced protein phosphorylation in VSMC was inhibited by 10 μmol·L -1 H L Lys and 10 mmol·L -1 L Arg by 31.8% and 37.4%, respectively ( P 0.01). Conclusion: NO and CO may have an inhibitive role against VSMC proliferation caused by bFGF, whose mechanism has a close relationship with inhibition of intracellular protein phosphorylation, PKC and MAPK activities stimulated by bFGF.