Enhancement of serum nitric oxide by Shichimotsu-koka-to (Kampo medicine).

The Kampo medicine Shichimotsu-koka-to (SKT) is used to treat hypertension and atherosclerosis in Japan. The action of SKT was studied, focusing on nitric oxide, which is intimately involved in regulation of blood pressure and cell functions associated with atherogenesis and inflammation. Oral administration of SKT enhanced serum nitric oxide (NOx) levels dose-dependently and 3 d administration was enough to detect its effect. The maximal level of serum NOx was maintained at around 27 microM, a concentration which did not result in harmful effects on cells. On the other hand, L-arginine, the substrate of NO synthase (NOS), was also increased by SKT administration. When the source of L-arginine was studied, only 12.7 mg of L-arginine was contained in 1 g of SKT and this amount of L-arginine could not explain the increased L-arginine levels in serum. These results suggest that SKT may enhance serum L-arginine by acting on L-arginine metabolism, but not by supplying L-arginine itself, resulting in enhancement of serum NOx. In conclusion, the antihypertensive and antiatherosclerotic action shown by SKT may be in part due to enhanced serum NOx, thus suggesting that SKT may become a unique orally active drug for cardiovascular diseases as a new NO donor.