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

Abstract

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 Ca 2+ -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 Ca 2+ channels on the vascular smooth muscle.

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

“…The exact compositions of crude drugs in three kampo formulations are summarized in Table 1. We have shown the same summary of compositions in previous article entitled "comparative study of vasodilatation induced by rokumigan, hachimijiogan, and goshajinkigan in the Rat aorta" of this journal [2].…”

“…To investigate the endothelium dependency of vasodilatations, L-NAME (100 μM) and endothelium removal were pretreated. In young rats, we have been reported that L-NAME and endothelium removal attenuated kampo formulations-induced vasodilatations in previous reports [2]. However, in aged rats, L-NAME and endothelium removal did not attenuate rokumigan-induced vasodilatations at 0.03 -1.0 mg/mL (Table 2).…”

“…The thoracic aorta was quickly removed, and was cut into rings of 3 mm in length. The experiments were carried ISSN: 2378-1343 out as reported previously [2,17,18,20]. The vascular rings were suspended between lower and upper triangular -shaped stainless steel stirrups in a jacketed organ chamber filled with 20 ml modified Krebs -Henseleit solution.…”

“…We ascribe partially these indications to the improvement of blood flow induced by these three Kampo formulations. We infer that these clinical indications are partially derived from the vasodilation induced by these Kampo formulations [2]. And these three Kampo formulations have same mechanisms of vasodilatation such as Ca 2+ channel inhibition, β-receptor activation and producing nitric oxide(NO) from endothelium [2].…”

Goshajinkigan increases peripheral capillary diameter in non‐diabetic and diabetic mice

“…Moreover, Nishida et al . demonstrated the vasodilatory effect of GJG on norepinephrine‐induced vasoconstriction in a concentration‐dependent manner in rat aorta through NO production [11]. These results strongly suggest that GJG could cause vasodilation via NO production in diabetic mice.…”