Physiological roles of K&lt;sup&gt;+&lt;/sup&gt; channels in vascular smooth muscle cells

Ko, Eun A.; Han, Jin; Jung, In Duk; Park, Won Sun

doi:10.1540/jsmr.44.65

Cited by 377 publications

(355 citation statements)

References 113 publications

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“…They are expressed widely in smooth muscle cells and play an important role in regulating vascular tone, which is activated by both membrane depolarization and intracellular calcium [19][20][21] . BK Ca channels have also been proposed as potential therapeutic targets for cardiovascular diseases because of their ability to regulate vascular tone [22,23] .…”

Section: Discussionmentioning

confidence: 99%

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

et al. 2015

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altitude diseases that are associated with significant morbidity and mortality, such as high-altitude pulmonary edema and heart diseases [3] . Echinacoside (ECH) (Figure 1) is a phenylethanoid glycoside found in a variety of Chinese herbs such as the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa [4,5] . Lagotis brevituba Maxim is a species of Lagotis spp belonging to the Scrophulariaceae and grows widely at an altitude over 3000 meter in the Qinghai-Tibet Plateau. ECH has various desirable pharmacological characteristics, such as antioxidative, anti-inflammatory, neuroprotective, hepatoprotective, and nitric oxide (NO) radical-scavenging properties [6] . It can also elicit endothelium-dependent relaxation in rat thoracic aortic rings and cure cardiovascular diseases [7] . HowEchinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BK Ca channels and reducing intracellular Ca 2+ levels Aim: Sustained pulmonary vasoconstriction as experienced at high altitude can lead to pulmonary hypertension (PH). The main purpose of this study is to investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa, on the pulmonary artery and its potential mechanism. Methods: Pulmonary arterial rings obtained from male Wistar rats were suspended in organ chambers filled with Krebs-Henseleit solution, and isometric tension was measured using a force transducer. Intracellular Ca 2+ levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM. Results: ECH (30-300 μmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a concentration-dependent manner, and this effect could be observed in both intact endothelium and endothelium-denuded rings, but with a significantly lower maximum response and a higher EC 50 in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl 2 . However, IMT, 4-AP, and Gli did not inhibit ECH-induced relaxation. Under extracellular Ca 2+ -free conditions, the maximum contraction was reduced to 24.54%±2.97% and 10.60%±2.07% in rings treated with 100 and 300 μmol/L of ECH, respectively. Under extracellular calcium influx conditions, the maximum contraction was reduced to 112.42%±7.30%, 100.29%±8.66%, and 74.74%±4.95% in rings treated with 30, 100, and 300 μmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean fluorescence intensity was lower in cells treated with ECH (100 μmol/L) than with NE. Conclusion: ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca 2+ levels, and induces its relaxation through the NO-cGMP pathway and opening of K + channels (BK Ca and K IR ).

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Section: Discussionmentioning

confidence: 99%

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

et al. 2015

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“…Therefore, the effect of β-adrenergic-mediated vasorelaxation was not involved in the pathway. K + channels play an important role in regulating resting arterial membrane potential and vascular tone [31][32][33] . The direct activation of K + channels on arterial smooth muscle cells generally hyperpolarizes the cell membrane, results in the inhibition of Ca 2+ influx through VDCC, and interrupts smooth muscle contraction.…”

Section: Discussionmentioning

confidence: 99%

Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta

et al. 2016

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Aim: Ginsenosides are considered to be the major pharmacologically active ginseng constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on isolated rat thoracic aortas as well as its vasorelaxant mechanisms. Methods: Aortic rings with or without endothelium were prepared from Wistar rats and suspended in organ-chambers. The changes in tension of the preparations were recorded through isometric transducers connected to a data acquisition system. The aortic rings were precontracted with phenylephrine (PE, 1 µmol/L) or high-K + (80 mmol/L).

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“…K + channel opening in the smooth muscle cell membrane causes K + efflux, resulting in hyperpolarization that closes the Cavs, resulting in decreased influx of Ca 2+ ions and thus, relaxation of the smooth muscles 25 . LEVO was able to induce vasodilatation in rings without functional endothelium with TEA, which suggests that these channels are not involved in LEVO-induced vasodilator effect.…”

Section: Discussionmentioning

confidence: 99%

Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery

Menezes

Souza

Santos

et al. 2016

Rev. odontol. UNESP

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ResumoIntrodução: Levobupivacaína pode ser uma nova alternativa para analgesia por apresentar baixa toxicidade e vasoconstrição, permitindo sua utilização em pacientes que apresentam contra-indicação no uso de vasoconstritores. Objetivo: Avaliar os efeitos da levobupivacaína utilizando a técnica de reatividade vascular em artéria mesentérica isolada de rato e comparar este efeito à lidocaína. Material e método: Anéis foram obtidos da artéria mesentérica de ratos machos Wistar e foram mantidos em cubas. Para o registro das contrações isométricas, cada anel foi suspenso por linhas de algodão fixadas a um transdutor de força acoplado a um sistema de aquisição. Resultado: Tanto a lidocaína como a levobupivacaína não apresentaram efeito vasocontritor sobre o tônus basal em anéis com endotélio functional. No entanto, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas induziram um vasorrelaxamento concentração-dependente. O efeito vasorrelaxante causado pela levobupivacaína não foi diferente após a remoção do endotélio, ou com o tetraetilamônio (1mM), um bloqueador não seletivo dos canais para. K + . Em anéis sem endotélio funcional e pré-contraídos com solução despolarizante de Tyrode (KCl 80mM), o vasorelaxamento induzido pela levobupivacaína não foi significativamente diferente daquele observado em anéis pré-contraídos com fenilefrina e não apresentou um efeito adicional significativo sobre o relaxamento máximo da nifedipina. Conclusão: Este estudo demonstrou que a levobupivacaína produz efeito vasorrelaxante em artéria mesentérica de rato, que é endotélio independente. Este efeito parece envolver os bloqueadores de canais para Ca 2+ em célula muscular vascular lisa.Descritores: Lidocaína; artéria mesentérica; vasodilatação. AbstractIntroduction: Levobupivacaine (LEVO) can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective: We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method: Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result: Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM), a non-selective K + channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode's solution (KCl 80 mM), LEVO-induced vasodilatation was not significantly differe...

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Physiological roles of K<sup>+</sup> channels in vascular smooth muscle cells

Cited by 377 publications

References 113 publications

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta

Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery

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