Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models

IF 1.5 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Clinical and Experimental Hypertension Pub Date : 2022-05-29 DOI:10.1080/10641963.2022.2079671

Imran Ul haq, T. Ahmad, T. Khan, A. Shah

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引用次数: 1

Abstract

ABSTRACT Background Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. Methods Phytolaccagenin was evaluated for its antihypertensive activity in rat models via in vivo and in vitro experiments using polyethylene tubings for cannulation, organ bath bubbled with carbogen gas, and a pressure transducer connected to a PowerLab data acquisition system. Results Intravenous administration of phytolaccagenin decreased mean arterial pressure (MAP), significantly, in normotensive and hypertensive anesthetized rats. Pretreatment of rats with atropine (2 mg/kg) partially reversed the decrease in blood pressure due to phytolaccagenin at first tested doses. However, Nω-nitro-L-arginine methyl ester (L-NAME) (100 mg/kg) pretreatment modified the effect of phytolaccagenin on blood pressure with greater response. In isolated rat aortic rings precontracted with phenylephrine, cumulative addition of phytolaccagenin induced relaxation that is ablated (50%) with denudation and pre-incubation with atropine (1 μM) and L-NAME (10 μM). Phytolaccagenin also partially inhibited high K+ precontraction at initial doses, while an inhibitory effect was observed at higher concentrations, confirming its effect on voltage-dependent calcium channels. In isolated spontaneously beating rat atrial strips, phytolaccagenin suppressed the atrial tone that was reduced with isoprenaline and atropine pre-incubation, suggesting the role of cardiac adrenergic and muscarinic receptors. Interestingly, atenolol (1 μM) pretreatment also ablated the cardiac effects of phytolaccagenin. Conclusion The antihypertensive effect of phytolaccagenin is due to a decrease in vascular resistance and cardiac depressant effects. These effects are mediated via muscarinic receptors-linked NO pathway, inhibitory effect on Ca2+ movements (vascular), and activation of cardiac muscarinic and blockade of β-adrenergic receptors.

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植物色素素在大鼠模型中的降压作用及其作用机制

摘要背景:植物绿原素是一种天然的三萜，据报道具有多种生物活性，表明其在高血压治疗中的潜在作用。方法采用聚乙烯管插管、含二氧化碳的器官浴、压力传感器连接PowerLab数据采集系统，通过体内和体外实验对植草青素在大鼠模型中的降压活性进行评价。结果静脉注射植草青素可显著降低正常和高血压麻醉大鼠的平均动脉压(MAP)。用阿托品(2mg /kg)预处理大鼠，在第一次试验剂量时，部分逆转了由植藻绿原素引起的血压下降。而ω-硝基- l -精氨酸甲酯(L-NAME) (100 mg/kg)预处理可以改善植藻青素对血压的影响，且效果更明显。在用苯肾上腺素预收缩的离体大鼠主动脉环中，累积添加植草青素诱导松弛，剥皮消融(50%)，并用阿托品(1 μM)和L-NAME (10 μM)预孵育。植藻绿原素在初始剂量下也部分抑制高K+预收缩，而在较高浓度下观察到抑制作用，证实了其对电压依赖性钙通道的作用。在离体自发跳动的大鼠心房条带中，植草球蛋白抑制了异丙肾上腺素和阿托品在孵育前降低的心房张力，提示心脏肾上腺素和毒蕈碱受体的作用。有趣的是，阿替洛尔(1 μM)预处理也能消除植藻绿原素对心脏的影响。结论植物色素原素的降压作用是由于其降低血管阻力和抑制心脏的作用。这些作用是通过毒蕈碱受体连接的NO途径、对Ca2+运动(血管)的抑制作用、心脏毒蕈碱的激活和β-肾上腺素能受体的阻断介导的。

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来源期刊

Clinical and Experimental Hypertension 医学-外周血管病

CiteScore

3.90

自引率

0.80%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.