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Autonomic nervous system mediates the cardiovascular effects of Rhodiola sacra radix in rats
Authors:Shih Cheng-Dean  Kuo Daih-Huang  Huang Chi-Wen  Gu Yu-Hua  Chen Fu-An
Institution:Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, 20 Weishin Road, Yanpu Township, Pingtung County 90741, Taiwan, ROC.
Abstract:ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola sacra (Crassulaceae) exhibits cardiovascular bioactivities and is used in Tibetan medicine for promoting circulation and preventing hypertension. However, the underlying mechanisms of its cardiovascular effects are poorly understood. AIM OF THE STUDY: The aim of this study was therefore to evaluate the cardiovascular activity of water-soluble fraction (WtF) and n-butanol-soluble fraction (BtF) of Rhodiola sacra radix and to explore its mechanism of action in propofol anesthetized Sprague-Dawley rats. MATERIALS AND METHODS: The changes of blood pressure, heart rate and cardiac contractility after systemic administration of the extracts (10-75mg/kg) were examined for at least 40min. Different antagonists were used to evaluate the mechanisms of cardiovascular effects of the extracts. RESULTS: Intravenous injection of the WtF (10, 25, 35, 50 or 75mg/kg) exhibited dose-dependent hypotension and increases in heart rate and cardiac contractility. In contrast, mild alterations in the same cardiovascular parameters were detected only at high dose (75mg/kg) BtF. The WtF-induced hypotensive, positive inotropic and chronotropic effects were significantly abolished by pretreatment with hexamethonium (30mg/kg, i.v.) or reserpine (5mg/kg, i.v.), whereas the hypotensive, but not the positive inotropic or chronotropic effect was potentiated by captopril (2.5mg/kg, i.v.). Pretreatment with methylatropine (1mg/kg, i.v.), on the other hand, reversed the positive inotropic and chronotropic but not the hypotensive effects of WtF. The WtF-induced cardiovascular responses were not affected in rats pretreated with N(G)-nitro-l-arginine methyl ester (20mg/kg, i.v.). CONCLUSIONS: We conclude that systemic administration of the WtF of Rhodiola sacra radix elicited a potent hypotensive effect that was mediated by the withdrawal of sympathetic vasomotor tone and interaction with the circulatory angiotensin system. The positive inotropic and chronotropic effects of WtF may result from a direct vagal inhibition on the heart.
Keywords:ACE  angiotensin converting enzyme  ACEI  ACE inhibitor  ANOVA  analysis of variance  BtF  n-butanol-soluble fraction  DBP  diastolic blood pressure  dP/dtmax  the maximal first derivative of developed pressure  HR  heart rate  L-NAME  NG-nitro-l-arginine methyl ester  MSAP  mean SAP  NO  nitric oxide  NOS  NO synthase  RAAS  renin–angiotensin–aldosterone system  SAP  systemic arterial pressure  SBP  systolic blood pressure  SNP  sodium nitroprusside  WtF  water-soluble fraction
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