Effects of Panax notoginseng saponins on vascular endothelial cells in vitro

To investigate the inhibition of endothelium-dependent in vitro vascular relaxation induced by the total saponins (gensenosides) from Panax notoginseng (PNS) and the effect of PNS on the cytosolic Ca2+ concentration on cultured bovine pulmonary artery endothelial cells. The endothelial-dependent vascular relaxation was assessed using acetylcholine (ACh) or cyclopiazonic acid (CPA) induced relaxation in endothelium-intact rat aorta. Cytosolic Ca2+ level was assessed in real time using dynamic digital fluorescence ratio imaging. In addition to its direct relaxation of the smooth muscle cells at high concentrations, PNS, at 100 mg/L having little effect on smooth muscle, caused a marked inhibition of endothelium-dependent relaxation brought about by PNS. This inhibitory effect was due to its inhibition of elevation of cytosolic Ca2+, which is required for the activation of NO generation and release from the vascular endothelial cells. Nifedipine has no effect on either the endothelium-dependent relaxation or the cytosolic Ca2+ level in the cultured endothelial cells. Our findings are consistent with the known action of PNS on receptor-operated Ca2+ channels and support our contention that PNS inhibits endothelium-dependent relaxation by preventing the increase of Ca2+ level in endothelial cells via the receptor-operated Ca2+ channels in the presence of ACh or the non-selective cation channels opened by CPA.