The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine growth retardation in preeclampsia rats induced by Nomega-nitro-L-arginine methyl ester.

The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial effects in this model. L-NAME was infused subcutaneously into pregnant rats from day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14 to 20. Systolic blood pressure was measured on day 19. On day 20, rats were sacrificed and serum NO levels, placental weight, fetal body weight, fetal cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1 g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS (2 g/kg). The effect of TS on blood pressure was found only in the rats that were both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to that contained in TS, showed no effect. Further, the change in serum NO levels induced by TS was only marginal. TS thus improved the hypertension and IUGR in preeclampsia rats induced by L-NAME in a NO-independent manner. These data suggested that TS may be beneficial for the treatment and prevention of preeclampsia.

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats.

We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.

An inhibitory effect of cytokine-induced neutrophil chemoattractant on corticotropin-releasing factor-induced increase in locomotor activity.

To investigate whether cytokine-induced neutrophil chemoattractant (CINC) has an influence on corticotropin-releasing factor (CRF) in the central nervous system, the effects of intracerebroventricular (i.c.v.) injection of CINC on CRF-induced behavior were examined. Intracerebroventricular CRF injection produced an increase in locomotor activity, which was significantly reduced by i.c.v. injection of CINC. The intravenous injection of CINC did not alter CRF-induced locomotor hyperactivity. These results suggested that CINC has a functional antagonistic action on the response to CRF and may attenuate stress responses.