Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hepatic Veno-Occlusive Disease/drug therapy , Thrombomodulin/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Hepatic Veno-Occlusive Disease/etiology , Humans , Infant , Male , Recombinant Proteins/therapeutic use , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Antihypertensive Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Phytotherapy , Plants, Medicinal , Pre-Eclampsia/drug therapy , Administration, Oral , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Female , Fetal Growth Retardation/drug therapy , Fetus/drug effects , Male , NG-Nitroarginine Methyl Ester , Nitric Oxide/blood , Pre-Eclampsia/chemically induced , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
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.
Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Hot Flashes/metabolism , Peptide Fragments/pharmacology , Receptors, Calcitonin Gene-Related Peptide/metabolism , Vasodilator Agents/pharmacology , Analysis of Variance , Animals , Calcitonin Gene-Related Peptide/blood , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide Receptor Antagonists , Dose-Response Relationship, Drug , Female , Hot Flashes/physiopathology , Humans , In Vitro Techniques , Mesenteric Arteries/metabolism , Mesenteric Arteries/physiopathology , Models, Animal , Ovariectomy , Protein Binding , Rats , Rats, Sprague-Dawley , Skin Temperature/drug effects , Vascular Resistance/drug effectsABSTRACT
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.
