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. 2016 Sep 1;14(1):254.
doi: 10.1186/s12967-016-1017-3.

Mechanisms Underlying the Antihypertensive Properties of Urtica Dioica

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Free PMC article

Mechanisms Underlying the Antihypertensive Properties of Urtica Dioica

Rahila Qayyum et al. J Transl Med. .
Free PMC article

Abstract

Background: Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension.

Methods: Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System.

Results: Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect.

Conclusions: These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

Keywords: Antihypertensive; Endothelium-dependent and-independent; Urtica dioica; Vasorelaxant.

Figures

Fig. 1
Fig. 1
A representative tracing a showing the effect of norepinephrine (NE), acetylcholine (Ach), and different doses of crude extract of U. dioica (Ud.Cr) on mean arterial pressure (MAP) in normotensive rats under anesthesia. b The hypertensive and hypotensive effects of norepinephrine (NE) and acetylcholine (ACh), respectively. c The blood pressure of normotensive and hypertensive rats. d The effect of crude extract of U. dioica (Ud.Cr) on MAP in normotensive and hypertensive rats, under anesthesia (n = 6–7), *p < 0.05, **p < 0.01, and ***p < 0.001 represent the significance difference between the % fall in MAP on normotensive and hypertensive rats
Fig. 2
Fig. 2
Graphs show the effect of a ethylacetate (Ud.EtAc) b nHexane (Ud.nHex), c chloroform (Ud.Chl) and d aqueous (Ud.Aq) fractions of U. dioica on mean arterial pressure (MAP) in normotensive and hypertensive rats, under anesthesia. Values shown are mean ± SEM (n = 6–7) *p < 0.05, **p < 0.01, and ***p < 0.001 represent the significance difference between the % fall in MAP on normotensive and hypertensive rats
Fig. 3
Fig. 3
af The response of crude extract of U. dioica (Ud.Cr), its fractions ethyl acetate (Ud.EtAc), nHexane (Ud.nHex), chloroform (Ud.Chl) and aqueous (Ud.Aq) and acetylcholine on PE-induced contractions in intact (with and without l-NAME (10 µM) pretreatment), denuded aortic rings from normotensive rats and rings from hypertensive rats. Values shown are mean ± SEM (n = 6–7), *p < 0.05, **p < 0.01, and ***p < 0.001
Fig. 4
Fig. 4
Graph shows a vasodilator effect of crude extract of U. dioica (Ud.Cr), its fractions ethyl acetate (Ud.EtAc), nHexane (Ud.nHex), chloroform (Ud.Chl) and aqueous (Ud.Aq) Ud.nHex, b verapamil on high K+ (80 mM)-induced contractions in isolated rat aorta rings. Values shown are mean ± SEM (n = 6–7), *p < 0.05, **p < 0.01, and ***p < 0.001 represent the significance difference between the relaxation of intact and denuded aorta
Fig. 5
Fig. 5
The graphs shows the concentration-dependent vasodilator effect of a crude extract of U. dioica (Ud.Cr), c the Verapamil on phenylephrine (PE) and high K+(80 mM) precontractions, bd respectively, their effect on the Ca2+ concentration–response curves, constructed in Ca2+- free medium, in isolated rabbit aorta preparations. Values shown are mean ± SEM (n = 6–7), *p < 0.05, **p < 0.01, and ***p < 0.001, represent the significance difference between the relaxation induced by phenylephrine (PE) and high K+ (80 mM)
Fig. 6
Fig. 6
The graphs shows the concentration-dependent vasodilator effect of ag crude extract of U. dioica (Ud.Cr), the Verapamil, ethyl acetate (Ud.EtAc), nHexane (Ud.nHex), chloroform (Ud.Chl), and aqueous (Ud.Aq) fractions on phenylephrine (PE) and high K+ (80 mM) precontractions, and (bh) respectively, their effect on the Ca2+ concentration–response curves, constructed in Ca2+- free medium, in isolated rabbit aorta preparations. Values shown are mean ± SEM (n = 6–7), *p < 0.05, **p < 0.01, and ***p < 0.001, represent the significance difference between the relaxation induced by phenylephrine (PE) and high K+ (80 mM)
Fig. 7
Fig. 7
Typical tracing showing inhibitory effect of a increasing concentrations of the crude extract of U. dioica (Ud.Cr) on the initial peak formation of phenylephrine in Ca2+-free medium. b The combined effect of Ud.Cr, its ethyl acetate (Ud.EtAc), nHexane (Ud.nHex), chloroform (Ud.Chl), and aqueous (Ud.Aq) fractions, and c the effect of verapamil on initial peak formation of PE in isolated rabbit aorta preparations, in Ca2+-free medium. Values shown are mean ± SEM (6–7)

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