The Effect of Herbal Medicine Toki-shakuyaku-san on Blood Pressure in an Nω-Nitro-L-Arginine Methyl Ester-Induced Pre-eclampsia Rat Model During Pregnancy and the Postpartum Period

The chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) in pregnant rats induces a pre-eclampsia-like syndrome, including hypertension. We have previously reported the beneficial effects of Toki-shakuyaku-san (TS) in this model. In the present study we demonstrated the anti-hypertensive effect of TS in pre-eclampsia produced by prolonged L-NAME-infusion during the postpartum period. Analysis of blood sex steroids suggested that the level of progesterone differs between the TS-effective (gestational day 19 and postpartum day 7) and TS-ineffective (postpartum day 1) periods. Co-administration of TS and progesterone inhibited L-NAME-induced hypertension on postpartum day 1. Furthermore, the anti-hypertensive effect of TS on postpartum day 6 disappeared in the presence of a co-administered progesterone antagonist mifepristone. These data suggest that a certain level of progesterone may be an indispensable prerequisite for an anti-hypertensive effect of TS. Finally, the effects of TS are apparently unrelated to blood levels of NO, calcitonin gene-related peptide, and endothelin-1, which have been reported to modulate systolic blood pressure in the L-NAME-induced pre-eclampsia model. Thus, the use of TS may provide a new therapeutic strategy for pre-eclampsia, although elucidation of the mechanism of action of TS would be necessary to optimize treatment protocols.