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      Teucrium polium-induced Vasorelaxation Mediated by Endothelium-dependent and Endothelium-independent Mechanisms in Isolated Rat Thoracic Aorta

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          Abstract

          Objective:

          There are some reports on hypotensive and antispasmodic effects of Teucrium polium L. ( Lamiaceae) (TP).

          Subjects and Methods:

          The activity of different concentrations of TP extract (1, 2, 4 and 8 mg/ml) was evaluated on contractile responses of isolated aorta to potassium chloride (KCl) and phenylephrine (PE).

          Results:

          The cumulative concentrations of the extract induced a concentration-dependent relaxation in the aorta precontracted by PE and KCl. Extract-induced vasorelaxations in denuded aortic rings precontracted by PE and KCl at lower concentrations were considerably less than intact aortic rings, but this effect was significantly more at concentrations of 4 mg/ml for PE-, 4 and 8 mg/ml for KCl-induced contractions. All the extract concentrations (except 1 mg/ml) significantly relaxed PE-induced contraction in the presence of N G-nitro-L-arginine methyl ester. Indomethacin reduced effectively extract-induced vasorelaxation at 1 and 2 mg/ml. The extract reduced PE- and KCl-induced contractions in the presence of cumulative calcium concentrations and after incubation with diltiazem; this vasorelaxant effect of TP was decreased. TP-induced relaxation was inhibited by heparin, ruthenium red, glibenclamide, and tetraethylammonium, but 4-aminopyridine had no effect on TP-induced relaxation.

          Conclusion:

          TP extract has vasorelaxant effect on isolated rat thoracic aorta which mediated by endothelium-dependent and endothelium-independent mechanisms. The relaxation mainly was mediated by inhibition of calcium influx in vascular smooth muscle cells. It seems that the vasorelaxant effect of extract at lower concentrations was mediated by nitric oxide and prostacyclin.

          SUMMARY

          • The vasodilatory effect of Teucrium polium L. was mediated by several mechanisms. First: Teucrium polium L. inhibited receptor operated ROCC and VDCC. Second: Teucrium polium L. also inhibited KATP and KCa channels. Third: Teucrium polium L. blocked IP3 receptor and reduced the release of calcium from intracellular source. Forth: Teucrium polium L. increased the release on NO and PGI2 from endothelial cells.

          Abbreviations Used: ROCC: Receptor operated calcium channels, VDCC: Voltage dependent calcium channels, PLC: Phospholipase C, IP3: 1,4,5 triphosphate inositol, IP3R: IP3 receptors, SR: sarcoplasmic reticulum, RYR: ryanodine receptors, K+ATP: ATP-sensitive potassium channel, K+Ca: Calcium-activated potassium channel, cAMP: Cyclic adenosine monophosphate, cGMP: Cyclic guanosine monophosphate, PGI2: Prostaglandin I2, NO: Nitric oxide

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          Most cited references43

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          Physiological roles and properties of potassium channels in arterial smooth muscle.

          This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.
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            Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture).

            Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. Endothelial dysfunction has been associated with a number of pathophysiological processes. Oxidative stress appears to be a common denominator underlying endothelial dysfunction in cardiovascular diseases. However, depending on the pathology, the vascular bed studied, the stimulant, and additional factors such as age, sex, salt intake, cholesterolemia, glycemia, and hyperhomocysteinemia, the mechanisms underlying the endothelial dysfunction can be markedly different. A reduced bioavailability of nitric oxide (NO), an alteration in the production of prostanoids, including prostacyclin, thromboxane A2, and/or isoprostanes, an impairment of endothelium-dependent hyperpolarization, as well as an increased release of endothelin-1, can individually or in association contribute to endothelial dysfunction. Therapeutic interventions do not necessarily restore a proper endothelial function and, when they do, may improve only part of these variables.
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              Physiological roles of K+ channels in vascular smooth muscle cells.

              In this review, we present the basic properties, physiological functions, regulation, and pathological alterations of four major classes of K+ channels that have been detected in vascular smooth muscle cells. Voltage-dependent K+ (Kv) channels open upon depolarization of the plasma membrane in vascular smooth muscle cells. The subsequent efflux of K+ through the channels induces repolarization to the resting membrane potential. Changes in the intracellular Ca2+ concentration and membrane depolarization stimulate large-conductance Ca2+-activated K+ (BKCa) channels, which are thought to play an important role in maintaining the membrane potential. ATP-sensitive K+ (K(ATP)) channels underscore the functional bond between cellular metabolism and membrane excitability. The blockade of KATP channel function results in vasoconstriction and depolarization in various types of vascular smooth muscle. Inward rectifier K+ (Kir) channels, which are expressed in smooth muscle of the small-diameter arteries, contribute to the resting membrane potential and basal tone. Kir channel activation has been shown to raise the extracellular K+ concentration to 10-15 mM, resulting in vasodilation. Each of K+ channels listed above is responsive to a number of vasoconstrictors and vasodilators, which act through protein kinase C (PKC) and protein kinase A (PKA), respectively. Impaired Kv, KATP, and Kir channel functions has been linked to a number of pathological conditions, which may lead to vasoconstriction.
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                Author and article information

                Journal
                Pharmacognosy Res
                Pharmacognosy Res
                PR
                Pharmacognosy Research
                Medknow Publications & Media Pvt Ltd (India )
                0976-4836
                0974-8490
                Oct-Dec 2017
                : 9
                : 4
                : 372-377
                Affiliations
                [1 ]Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [3 ]Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                [4 ]Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                Correspondence: Dr. Maryam Mahmoudabady, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Post Code 9177948564, Iran. E-mail: mahmoudabadym@ 123456mums.ac.ir
                Article
                PR-9-372
                10.4103/pr.pr_140_16
                5717790
                8991650d-ada6-403b-912a-87a35266b079
                Copyright: © 2017 Pharmacognosy Research

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                calcium channels,isolated aorta,potassium channels,teucrium polium,vasorelaxation

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