Age-Dependent Change of Ro-kumigan, Hachimijiogan and Goshajinkigan-Induced Vasodila- tations in Rat Aorta

Background: Rokumigan, hachimijiogan and goshajinkigan are traditional Kampo formulations. These formulations are considered to be useful for edema, water disturbance, and urinary problem. Rokumigan is composed of six kinds of crude herbal drugs. Hachimijiogan comprises the same six kinds of herbs and two crude drugs and goshajinkigan includes the same eight herbs of hachimijiogan and two others. We demonstrated that these formulations possess vasodilating actions in rat aorta. Traditionally, rokumigan is thought to be useful for young persons, while hachimijiogan and goshajinkigan are thought to be for elderly persons. In this study, we compare the age-dependent modulation of these Kampo formulations. Methods: Young wistar rats (10 to 15 week old) and aged rats (35 to 40 week old) were used to investigate the age-dependent actions of these formulations. The isolated aorta ring strips were fixed in Krebs-Henseleit solution. After the contractile response induced by norepinephrine became steady, Kampo formulations are added. Results: Rokumigan showed potent vasodilatation in young rats. However, the vasodilation - induced by rokumigan was attenuated in aged rats. On the contrary, hachimijiogan - induced vasodilatation in aged rats was to the same extent as that in young rats. Furthermore, compared with young rats, goshajinkigan - induced vasodilatation significantly increased in aged rats. Endothelium removal and L-NAME(NO synthase inhibitor) attenuated rokumigan, hachimijiogan and goshajinkigan - induced vasodilatation in young rats. However, endothelium removal and the pretreatment of L-NAME did not modify rokumigan - induced vasoditation in aged rats. Endothelium removal and L-NAME attenuated hachimijiogan and goshajinkigan - induced vasodilatation in aged rats. Conclusion: Rokumigan - induced vasodilatation attenuated as age, while the potency of hachimijiogan and goshajinkigan - induced vasodilatations was not changed or increased in aged rats compared with young rats. Our results suggested that the difference of age - related dependency of kampo formulations on vasodilatation was derived from their different dependency to the endothelium.