Abstract
Natural products, which have been used for the treatment of hypertension, diuresis and nephritis in traditional oriental medicine, were selected for the screening of nitric oxide (NO) production in endothelial cells and kidney tissues in vitro as well as in vivo by measuring the conversion of [$\^$14/C]-L-arginine to [$\^$14/C]-L-citrulline, a coproduct of the enzyme reaction with NO. Confluent monolayer of endothelial cells were used for the screening of 16 natural products. Among the natural products, Zizyphus jujuba and Codonopsis pilosula stimulated endothelial NO synthase activity. Thus, both confluent monolayer of endothelial cells and kidney homogenates (glomeruli, cortical tubules, meudllae) were treated with Zizyphus jujuba and Codonopsis pilosula (final concentration 10 $\mu\textrm{g}$/$m\ell$) and NO releases were compared with those by receptor - dependent agonists, bradykinin and ADP and receptor - independent calcium ionophore A23187 in vitro. In rat experiment, NO releases in glomeruli, cortical tubules and medullae and plasma renin activity were assessed after intraperitoneal injection of Zizyphus jujuba and Codonopsis pilosula (10 mg/kg/day for 4 days). As a result, both Zizyphus jujuba and Codonopsis pilosula significantly increased NO releases in cultured endothelial cells, kidney tissues in vitro as well as in vivo. Stimulation of NO releases by Zizyphus jujuba and Codonopsis pilosula was similar to those by receptor - dependent agonists, bradykinin and ADP and receptor - independent calcium ionophore A23187 in cultured endothelial cells. However, plasma renin activity was not influenced by these two natural products. In conclusion, stimulatory effects of Zizyphus jujuba and Codonopsis pilosula on NO release in kidney may contribute their hypotensive effects and antinephritic action possibly by increasing renal blood flow.
(Department of Urology, Yonsei University School of Medicine)