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利尿剂草药鸡冠花(苋科)促进持续的动脉血压降低,并防止肾血管性高血压大鼠的心脏重构。

Diuretic herb Gomphrena celosioides Mart. (Amaranthaceae) promotes sustained arterial pressure reduction and protection from cardiac remodeling on rats with renovascular hypertension.

机构信息

College of Health Science, Federal University of Grande Dourados, Dourados, MS, Brazil.

Institute of Biology, Department of Plant Biology, PPG BTPB, Faculty of Pharmaceutical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil.

出版信息

J Ethnopharmacol. 2018 Oct 5;224:126-133. doi: 10.1016/j.jep.2018.05.036. Epub 2018 May 26.

DOI:10.1016/j.jep.2018.05.036
PMID:29842964
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Gomphrena celosioides Mart., belonging to the Amaranthaceae family, is a weed known as "perpétua," and its ethnopharmacological use is to treat of urinary tract disorders and kidney stones. Urinary tract disorders and kidney stones could include several pathological conditions such hypertension, diuretic and lithiasic problems. In the present work a model of renovascular hypertension was developed in vivo to investigate its usefulness as an antihypertensive drug.

AIM OF THE STUDY

Evaluate the effect of acute and 28 day oral administration of G. celosioides extract on systemic arterial pressure and diuresis of renovascular-hypertensive rats, as well as its effect on cardiac remodeling and vascular reactivity.

MATERIALS AND METHODS

Ethanolic extract of G. celosioides (EEGC) was used. To induce renovascular hypertension, adult male Wistar rats were submitted to Goldblatt 1K1C or 2K1C surgery. The mean arterial pressure (MAP) of 1K1C animals was directly assessed by cannulation of the carotid artery before and after intraduodenal acute administration of 30, 100 or 300 mg/kg of EEGC. For the 4-week assay, 2K1C animals received daily treatments with water (control group), 100 mg/kg EEGC or 15 mg/kg enalapril for 28 days. Diuresis and caudal blood pressure were assessed weekly, and at the 28th day of treatment, the MAP was directly quantified shortly before euthanasia. Internal organs were removed, weighed and routinely processed for histology and the left ventricle wall was measured. Blood was collected for biochemical analysis and mechanism investigation by quantification of angiotensin converting enzyme (ACE) activity and aldosterone, nitrite and thiobarbituric acid reactive substances (TBARS) concentration. The rats' mesenteric beds were isolated and cannulated to have their pressure variation assessed after crescent doses of phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside (SNP).

RESULTS

EEGC acutely reduced MAP the dose of 100 mg/kg. In the 4-week assay, EEGC acted as diuretic after acute administration after 1, 2, 3 and 4 weeks of treatment. EEGC also acted as an antihypertensive and it showed significant difference already after 1 week (and after 3 and 4 weeks) compared to control, with its MAP close to pre-surgery values at the end of the experiment. It promoted ACE inhibition, which led to lower aldosterone levels. The lower TBARS and higher nitrite concentration found in the EEGC group suggest antioxidant activity and NO maintenance. Moreover, EEGC counteracted the impairment of vascular reactivity induced by renovascular hypertension. The extract group presented thinner left ventricle wall compared to the control, meaning reduced hypertension-induced cardiac remodeling.

CONCLUSIONS

The G. celosioides diuretic effect is maintained on renovascular hypertensive rats and can reduce the blood pressure after the first week of treatment by inhibiting ACE and these effects are longstanding and strong enough to promote protection against cardiac remodeling. Therefore, it shows potential as an antihypertensive drug.

摘要

民族药理学相关性

Gomphrena celosioides Mart.,属于苋科,是一种被称为“perpétua”的杂草,其民族药理学用途是治疗尿道疾病和肾结石。尿道疾病和肾结石可能包括高血压、利尿剂和结石等几种病理状况。在目前的工作中,体内建立了肾血管性高血压模型,以研究其作为抗高血压药物的用途。

研究目的

评估急性和 28 天口服 G. celosioides 提取物对肾血管性高血压大鼠全身动脉压和利尿作用的影响,以及对心脏重构和血管反应性的影响。

材料和方法

使用 G. celosioides 的乙醇提取物(EEGC)。为了诱导肾血管性高血压,成年雄性 Wistar 大鼠接受 Goldblatt 1K1C 或 2K1C 手术。在经十二指肠给予 30、100 或 300mg/kg EEGC 前后,通过对颈总动脉进行插管直接评估 1K1C 动物的平均动脉压(MAP)。在 4 周试验中,2K1C 动物每天接受水(对照组)、100mg/kg EEGC 或 15mg/kg 依那普利治疗 28 天。每周评估利尿作用和尾血压,在治疗的第 28 天,在安乐死前短时间内直接量化 MAP。取出内脏器官,称重并常规进行组织学处理,测量左心室壁。收集血液进行生化分析和机制研究,包括血管紧张素转换酶(ACE)活性和醛固酮、亚硝酸盐和硫代巴比妥酸反应物质(TBARS)浓度的定量。分离肠系膜床并进行插管,以评估酚妥拉明(Phe)、乙酰胆碱(ACh)和硝普钠(SNP)递增剂量后的压力变化。

结果

EEGC 急性降低 MAP 的剂量为 100mg/kg。在 4 周试验中,EEGC 在急性给药后 1、2、3 和 4 周均具有利尿作用。EEGC 还具有抗高血压作用,与对照组相比,它在第 1 周(第 3 周和第 4 周)后就表现出显著差异,实验结束时其 MAP 接近术前值。它促进 ACE 抑制,导致醛固酮水平降低。EEGC 组发现较低的 TBARS 和较高的亚硝酸盐浓度表明具有抗氧化活性和维持 NO。此外,EEGC 对抗了肾血管性高血压引起的血管反应性损害。与对照组相比,提取物组的左心室壁较薄,这意味着高血压引起的心脏重构减少。

结论

G. celosioides 的利尿作用在肾血管性高血压大鼠中得以维持,并且可以在治疗的第一周后降低血压,其机制是抑制 ACE,这些作用持久且强大,足以促进对心脏重构的保护。因此,它具有作为抗高血压药物的潜力。

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