The effect of herbal medicine Toki-shakuyaku-san on blood pressure in an Nomega-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.
Takei
Hisato
H
Tsumura Research Institute, Tsumura and Co., Ibaraki, Japan. takei_hisato@mail.tsumura.co.jp
Yamamoto
Masahiro
M
Kase
Yoshio
Y
Takeda
Shuichi
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004958:Estradiol / Q000097:blood; D005260:Female; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; C413220:toki-shakuyaku-san; D009569:Nitric Oxide; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester