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

• Published in: Clinical and experimental hypertension (1993) 2022-08, Vol.44 (6), p.557-566
• Main Authors: Ul Haq, Imran, Ahmad, Taseer, Khan, Taous, Shah, Abdul Jabbar
• Format: Article
• Language: English
• Subjects: antihypertensive; calcium movement; muscarinic; nitric oxide; Phytolaccagenin; β- receptors
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1080/10641963.2022.2079671

Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. 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. 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. 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 Ca 2+ movements (vascular), and activation of cardiac muscarinic and blockade of β-adrenergic receptors.