Comparative Study of Vasodilatation Induced by Rokumigan, Hachimijiogan, and Goshajinkigan in the Rat Aorta

Rokumigan, hachimijiogan, and goshajinkigan are traditional Japanese Kampo formulations with similar components and consequently similar clinical indications. These formulations are considered useful for the management of edema, water disturbances, dry skin, dry mouth, and abnormal urination. Rokumigan is composed of six types of crude herbal drugs, hachimijiogan comprises rokumigan and two crude drugs, and goshajinkigan includes hachimijiogan and two other crude drugs. In this study, we compared the vasodilatations induced by these formulations and investigated the underlying mechanisms using rat aortic ring strips. We found that 0.1 to 3.0 mg/ mL of these formulations counteracted the effects norepinephrine (5 μM)-induced vasoconstriction in a concentration dependent manner. The vasodilatation induced by 0.03 to 1.0 mg/mL of the formulations was similar, although rokumigan induced the greatest vasodilatation at 3.0 mg/mL. Pretreatment with L-NAME (100 μM) and endothelium removal significantly attenuated the vasodilatation induced by the three formulations, whereas indomethacin (10 μM) showed no effects.Furthermore, pretreatments with propranolol (3 μM) and nicardipine (2 μM) markedly decreased this vasodilatation, which was also observed in Ca2+-free solution. These results indicate that rokumigan, hachimijiogan, and goshajinkigan induce marked vasodilatation via nitric oxide production from the endothelium and via β-adrenoceptor stimulation and blockade of L-type Ca2+ channels on the vascular smooth muscle.