EFFECT OF NOTOGINSENOSIDE R1 ON THE SYNTHESIS OF COMPONENTS OF THE FIBRINOLYTIC SYSTEM IN CULTURED SMOOTH-MUSCLE CELLS OF HUMAN PULMONARY-ARTERY

We have previously reported that notoginsenoside R1 (NG-R1) increases the synthesis of tissue-type plasminogen activator (t-PA) and decrease s plasminogen activator inhibitor-1 (PAI-1) activity in cultured human endothelial cells from different vascular sources. It was the aim of this study to investigate whether the effect of NG-R1 on the synthesis of components of the fibrinolytic system is also operative in another cell type of the blood vessel wall, the smooth muscle cell. Therefore cultured human pulmonary artery smooth muscle cells (HPASMCs) were tr eated with NG-R1. When the HPASMCs (passage 4 or 5) were conditioned w ith NG-R1, a dose (0.01-100 mu g NG-RL/ml for 24 hrs.) dependent incre ase in t-PA and u-PA synthesis was observed, which was significant fro m 1 mu g NG-R1/ml on. t-PA antigen increased from 2.4+/-0.1 to 4.7+/-0 .5 ng/10(5) cells/24 hrs.; u-PA antigen increased from 1.8+/-0.1 to 3. 0+/-0.4 ng/10(5) cells/24 hrs. In contrast no change in PAI-1 antigen synthesis was seen in the conditioned media from NG-R1 treated HPASMCs . On Northern blot analysis of mRNA obtained from NG-R1-stimulated and control HPASMCs NG-R1 induced a significant increases in mRNA levels of t-PA and u-PA (180% and 200% of control value, respectively) at 100 mu g NG-R1/ml while PAI-I mRNA decreased slightly. In conclusion our data give evidence that NG-R1 can increase the fibrinolytic potential in cultured HPASMCs in vitro by increasing the production of t-PA and u-PA. If operative in vivo this effect of NG-R1 on the fibrinolytic sy stem of SMCs might also contribute to the effect of the Chinese herb d rug Panax notoginseng in the treatment of cardiovascular diseases.