Juglone as antihypertensive agent acts through multiple vascular mechanisms

Background: Juglone, a natural phenolic compound obtained from the walnut tree, is known for its wide range of biological activities. However, it has yet to be tested for its effects on hypertension and vascular tone. This investigation was aimed to explore the antihypertensive effect and the nature of vascular reactivity of juglone in rat models.Methods: Juglone was tested in in vivo and in vitro experiments in rats. The responses were analyzed and recorded through a PowerLab data acquisition system.Results: Intravenous injection of juglone significantly decreased the mean arterial blood pressure (MAP) in normotensive and hypertensive rats (Max. fall, 43.50 ± 2.96 vs 49.66 ± 3.28 mmHg). In rats pretreated with Nω-Nitro l-arginine methyl ester (_L-NAME), the effect of juglone on MAP was reduced as compared to the control. However, in rats pretreated with atropine the fall in MAP by juglone was not altered. Juglone induced relaxation in the phenylephrine, K⁺ (80 mM), and angiotensin II pretreated isolated rat aortic rings. This vasorelaxant effect was reduced with _L-NAME pretreatment. Atropine pretreatment did not modify the vasorelaxant effect of juglone. Pre-incubation with juglone attenuated the intracellular Ca²⁺ release by suppressing phenylephrine peak formation and also shifted CaCl₂ concentration-response curves (CRCs) to the right. Of note, combined treatment with 4-aminopyridine and barium chloride also reduced juglone-mediated vasorelaxation suggesting a role of K⁺-channels as well.Conclusion: In conclusion, juglone exerts its antihypertensive effect through vasorelaxation, which is mediated by nitric oxide, inhibition of intracellular calcium release and opening of K⁺-channels.