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姜黄甲醇提取物对大鼠的降压及非内皮依赖性血管舒张作用。

Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats.

作者信息

Adaramoye Oluwatosin A, Anjos Raline M, Almeida Mônica M, Veras Robson C, Silvia Darìzy F, Oliveira Francisco A, Cavalcante Karla V, Araújo Islania G, Oliveira Aldeìdia P, Medeiros Isac A

机构信息

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Brazil.

出版信息

J Ethnopharmacol. 2009 Jul 30;124(3):457-62. doi: 10.1016/j.jep.2009.05.021. Epub 2009 May 27.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Curcuma longa L. (CL) is a yellow rhizome that is used in African traditional medicine to treat palpitation, hypertension or other related blood circulation disorders.

AIM OF THE STUDY

To justify the use of CL in ethnomedicine, we investigated the vasorelaxant effect of methanolic extract of CL (CLME) and its underlying mechanisms in isolated rat mesenteric artery.

MATERIALS AND METHODS

The effect of CLME on the mean arterial pressure (MAP) and heart rate (HR) (pulse interval) were determined in vivo in non-anaesthetized rats. Superior mesenteric rings were isolated, suspended in organ baths containing Tyrode solution at 37 degrees C and gassed with 95% O(2)+5% CO(2), under a resting tension of 0.75 g. The vasorelaxant effects of CLME were studied by means of isometric tension recording experiments.

RESULTS

In normotensive rats, CLME (10, 20 and 30 mg/kg, i.v.) induced dose-dependent hypotension (2.0+/-0.5%; 27.1+/-5.0% and 26.7+/-4.6%, respectively), and pronounced bradycardia (5.8+/-1.2%, 19.3+/-3.2% and 22.9+/-4.6%, respectively). CLME (1-1000 microg/mL) induced concentration-dependent relaxation of tonic contractions evoked by phenylephrine (Phe) (10 microM) and KCl (80 mM) in rings with intact-endothelium (E(max)=82.3+/-3.2% and 97.7+/-0.7%) or denuded-endothelium (E(max)=91.4+/-1.0% and 97.8+/-1.1%). Also, in a depolarized, Ca(2+) free medium, CLME inhibited CaCl(2) (1 microM-30 mM)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that CLME inhibited the contractile mechanisms involving extracellular Ca(2+) influx. In addition, in Ca(2+) free media containing EGTA (1 mM), CLME inhibited the transient contraction of denuded rings constricted with Phe, but not those evoked by caffeine (20 mM). In contrast, neither glibenclamide, BaCl(2), tetraethylammonium nor 4-aminopyridine affected CLME-induced relaxation.

CONCLUSIONS

These results demonstrate the hypotensive and bradycardic effects of CLME, as well as its potent vasodilation of rat mesenteric arteries. These effects, may in part, be due to the inhibition of extracellular Ca(2+) influx and/or inhibition of intracellular Ca(2+) mobilization from Phe-sensitive stores.

摘要

民族药理学相关性

姜黄是一种黄色根茎,在非洲传统医学中用于治疗心悸、高血压或其他相关血液循环障碍。

研究目的

为了证明姜黄在民族医学中的应用合理性,我们研究了姜黄甲醇提取物(CLME)对离体大鼠肠系膜动脉的血管舒张作用及其潜在机制。

材料与方法

在未麻醉的大鼠体内测定CLME对平均动脉压(MAP)和心率(HR)(脉搏间期)的影响。分离出肠系膜上动脉环,悬挂于含37℃台氏液的器官浴槽中,通入95%O₂+5%CO₂,静息张力为0.75g。通过等长张力记录实验研究CLME的血管舒张作用。

结果

在正常血压大鼠中,CLME(10、20和30mg/kg,静脉注射)引起剂量依赖性低血压(分别为2.0±0.5%、27.1±5.0%和26.7±4.6%)和明显的心动过缓(分别为5.8±1.2%、19.3±3.2%和22.9±4.6%)。CLME(1 - 1000μg/mL)在完整内皮(E(max)=82.3±3.2%和97.7±0.7%)或去内皮(E(max)=91.4±1.0%和97.8±1.1%)的血管环中,能引起由去氧肾上腺素(Phe)(10μM)和氯化钾(80mM)诱发的张力性收缩的浓度依赖性舒张。此外,在去极化的无钙培养基中,CLME抑制氯化钙(1μM - 30mM)诱导的收缩,并使反应曲线浓度依赖性右移,表明CLME抑制了涉及细胞外钙内流的收缩机制。另外,在含乙二醇双四乙酸(EGTA)(1mM)的无钙培养基中,CLME抑制了用Phe收缩的去内皮血管环的瞬时收缩,但不抑制咖啡因(20mM)诱发的收缩。相反,格列本脲、氯化钡、四乙铵和4 - 氨基吡啶均不影响CLME诱导的舒张。

结论

这些结果证明了CLME的降压和心动过缓作用,以及其对大鼠肠系膜动脉的强力血管舒张作用。这些作用可能部分归因于对细胞外钙内流的抑制和/或对去氧肾上腺素敏感储存库中细胞内钙动员的抑制。

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