Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

Senadheera, Sevvandi; Kim, Youngsoo; Grayson, T. Hilton; Toemoe, Sianne; Kochukov, Mikhail Y.; Abramowitz, Joel; Housley, Gary D.; Bertrand, Rebecca L.; Chadha, Preet S.; Bertrand, Paul; Murphy, Timothy V.; Tare, Marianne; Birnbaumer, Lutz; Marrelli, Sean P.; Sandow, Shaun L.

doi:10.1093/cvr/cvs208

Cited by 77 publications

(77 citation statements)

References 55 publications

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“…To test the involvement of TRPC3 in the acetylcholine-induced, EDH-mediated relaxation, we used Pyr3 (10 −6 mol/L), which have been reported to block TRPC3 selectively. 33 Blockade of TRPC3 with Pyr3 significantly inhibited the EDH-mediated relaxation in both the WKY and SHRSP preparations (Figure S3A and S3B; Table S1). In mesenteric arteries freshly isolated from WKY and SHRSP, there was no significant difference in TRPC3 protein expression level between the WKY and SHRSP groups (Figure S3C and S3D; n=4 each).…”

Section: Function and Expression Of Trpc3 Channel In Mesenteric Arterymentioning

confidence: 93%

“…33 Thus, it is possible to speculate that the alteration in the function and expression of TRPC3 is involved in the impaired EDH-mediated responses in the mesenteric artery of SHRSP. However, such a possibility seems unlikely in the present study: first, because acetylcholine-induced, EDHmediated relaxations were reduced by the blockade of TRPC3 with the selective antagonist Pyr3 not only in the WKY but also in the SHRSP groups.…”

Section: Seki Et Al Downregulation Of Trpv4 Channel In Hypertension 151mentioning

confidence: 99%

“…Because TRPC3 has been demonstrated to play a critical role in EDH-mediated responses in rat mesenteric arteries, 33 we examined whether TRPC3 is involved in the impaired EDHmediated responses in mesenteric arteries of SHRSP. To test the involvement of TRPC3 in the acetylcholine-induced, EDH-mediated relaxation, we used Pyr3 (10 −6 mol/L), which have been reported to block TRPC3 selectively.…”

Section: Function and Expression Of Trpc3 Channel In Mesenteric Arterymentioning

confidence: 99%

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Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

et al. 2017

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V ascular endothelial cells play an important role in the regulation of vascular tone through the release of both vasorelaxing and vasoconstricting factors.1 Apart from the release of vasorelaxant factors such as nitric oxide and prostaglandins, endothelial cells relax the vascular smooth muscle cells through the generation of endothelium-dependent hyperpolarization (EDH). With respect to EDH, there is consensus that the activation of the small-and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca ) located on endothelial cells results in the generation of EDH. [2][3][4][5][6][7][8] In rat mesenteric arteries, the electric transmission of EDH to the adjacent smooth muscle cells via myoendothelial gap junctions (MEGJs) plays a central role in EDH-mediated responses. [9][10][11] Several recent studies have suggested that Ca 2+ influx through endothelial transient receptor potential vanilloid 4 channel (TRPV4), a member of the TRP family of nonselective cation channels, plays a crucial role in EDHmediated hyperpolarization via the downstream activation of SK Ca and IK Ca in specific beds. 12,13 Although the mechanisms through which TRPV4 interact with SK Ca /IK Ca are not well understood, recent studies have suggested that, in specific beds, Ca 2+ influx through TRPV4 directly activates nearby IK Ca and SK Ca at the myoendothelial microdomain signaling sites to generate EDH. 12.13 In rat mesenteric arteries, it has been reported that the relative contribution of EDH in the acetylcholine-induced relaxations decreases as the vessel size increases.14 Although some previous studies reported little or no EDH-mediated relaxations in the superior mesenteric arteries of the rat, 15,16 acetylcholine evoked robust and consistent EDH-mediated Abstract-Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca , using isolated superior mesenteric arteries of 20-week-old strokeprone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDHmediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl) diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, we...

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Section: Function and Expression Of Trpc3 Channel In Mesenteric Arterymentioning

confidence: 93%

Section: Seki Et Al Downregulation Of Trpv4 Channel In Hypertension 151mentioning

confidence: 99%

Section: Function and Expression Of Trpc3 Channel In Mesenteric Arterymentioning

confidence: 99%

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Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

et al. 2017

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“…These initial observations have since been confirmed by other groups, identifying channels from the TRP family as the molecular protein responsible for extracellular calcium influx. Namely, the isoforms TRPV1, TRPV3, TRPV4, TRPC3, and TRPC1 have all been reported in the EDH-mediated response (Kohler and Hoyer, 2007;Loot et al, 2008;Earley et al, 2009;Schmidt et al, 2010;Senadheera et al, 2012;Ma et al, 2013).…”

Section: B Potassium and Calcium Channels: A Case For The Endotheliumentioning

confidence: 99%

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

et al. 2014

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“…TRPC1/TRPC3 channels were found to be present in freshly isolated VSMCs, were inhibited by the NO/cGMP/PKG pathway and contributed to NO-induced vasodilatation [51]. TRPC3 was also detected in human and rodents' vascular ECs and facilitated endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity [52,53]. TRPC4 proteins have also been identified as indispensable components of storeoperated Ca 2+ channels in mouse aortic ECs, as agonist-activated Ca 2+ entry into TRPC4-deficient ECs was found to be drastically decreased, leading to a dramatically impaired endothelium-dependent relaxation [54].…”

Section: Trp Channels Contribute To Vasodilatationmentioning

confidence: 99%

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension

Liu

Xiong

Zhu

2014

Sci. China Life Sci.

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Intracellular Ca 2+ homeostasis is essential for vascular function and blood pressure regulation. Because of their unique roles in regulating intracellular Ca 2+ concentration and vascular function, a novel class of non-selective cation channels, called transient receptor potential (TRP) channels, have emerged at the frontier of hypertension research. Based on their role in vasculature function regulation, TRP channels can be divided into two functional subtypes: one that participates in vasoconstriction and one that participates in vasodilatation. A functional imbalance of these two subtypes of TRP channels may disturb intracellular calcium ([Ca 2+ ]i) homeostasis, and the consequent vascular dysfunction may contribute to the development of hypertension. The potential of these TRP channels as novel pharmacological targets for the treatment of human hypertension is of great interest. TRP channels, Ca 2+ homeostasis, vascular function, hypertension Citation:Liu DY, Xiong SQ, Zhu ZM. Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension. Sci China Life Sci, 2014, 57: 818 -825,

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Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

Cited by 77 publications

References 55 publications

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension

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Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

Cited by 77 publications

References 55 publications

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca 2+ -Activated K + Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca 2+ -Activated K + Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension

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About

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca ²⁺ -Activated K ⁺ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension