Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo

Pozsgai, Gábor; Bodkin, Jennifer V.; Graepel, Rabea; Bevan, Stuart; Andersson, David A.; Brain, Susan D.

doi:10.1093/cvr/cvq118

Cited by 117 publications

(133 citation statements)

References 38 publications

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“…Finally, we investigated whether 4-ONE can, like the exogenous agonists mustard oil and cinnamaldehyde (Pozsgai et al, 2010), influence peripheral blood flow in vivo. We have shown previously that activation of TRPV1 by capsaicin triggers neurogenic vasodilatation in the mouse in vivo (Grant et al, 2002;Starr et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The effect of 10 nmol 4-ONE on hind paw blood flow was investigated. Previous studies have shown that topical application of mustard oil induces a potent TRPA1-dependent vasodilatation (Pozsgai et al, 2010), but 4-ONE is not absorbed into the skin via topical application. Here, intraplantar injections of 50 l of 4-ONE or vehicle were given into either hind paw, and plantar blood flow was measured for 30 min.…”

Section: -One Induces Dose-and Time-dependent Mechanical Hyperalgesimentioning

confidence: 97%

“…Several TRPA1 agonists have been shown to trigger acute pain behaviors, hyperalgesia and neurogenic inflammation in animal and human studies (Eid et al, 2008). Our most recent evidence shows that mustard oil and cinnamaldehyde induce neurogenic vasodilatation in mouse skin that is TRPA1-dependent (Pozsgai et al, 2010). Far less is known about the potential of lipid peroxidation products to act as endogenous mediators of TRPA1-dependent peripheral responses.…”

Section: Introductionmentioning

confidence: 99%

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4-Oxo-2-nonenal (4-ONE): Evidence of Transient Receptor Potential Ankyrin 1-Dependent and -Independent Nociceptive and Vasoactive Responses In Vivo

Graepel

Fernandes²,

Aubdool

et al. 2011

J Pharmacol Exp Ther

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This study explores the in vivo effects of the proposed transient receptor potential ankyrin 1 (TRPA1) agonist 4-oxo-2-nonenal (4-ONE). Pharmacological inhibitors and genetically modified mice were used to investigate the ability of 4-ONE to act via TRPA1 receptors and possible mechanisms involving transient receptor potential vanilloid 1 (TRPV1). We hypothesized that 4-ONE activates sensory nerves, via TRPA1 or possibly TRPV1, and thus triggers mechanical hyperalgesia, edema formation, and vasodilatation in mice. An automated dynamic plantar aesthesiometer was used to determine hind paw withdrawal thresholds, and a laser Doppler flowmeter was used to measure skin blood flow. Edema formation was determined by measuring paw weights and thickness. 4-ONE (10 nmol) triggers unilateral mechanical hyperalgesia, edema formation, and vasodilatation in mice and is shown here to exhibit TRPA1-dependent and -independent effects. Neurogenic vasodilatation and mechanical hyperalgesia at 0.5 h postinjection were significantly greater in TRPA1 wild-type (WT) mice compared with TRPA1 knockout (KO) mice. Edema formation throughout the time course as well as mechanical hyperalgesia from 1 to 4 h postinjection were similar in WT and TRPA1 KO mice. Studies involving TRPV1 KO mice revealed no evidence of TRPV1 involvement or interactions between TRPA1 and TRPV1 in mediating the in vivo effects of 4-ONE. Previously, 4-ONE was shown to be a potent TRPA1 agonist in vitro. We demonstrate its ability to mediate vasodilatation and certain nociceptive effects in vivo. These data indicate the potential of TRPA1 as an oxidant sensor for vasodilator responses in vivo. However, 4-ONE also triggers TRPA1-independent effects that relate to edema formation and pain.

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Section: Discussionmentioning

confidence: 99%

Section: -One Induces Dose-and Time-dependent Mechanical Hyperalgesimentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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4-Oxo-2-nonenal (4-ONE): Evidence of Transient Receptor Potential Ankyrin 1-Dependent and -Independent Nociceptive and Vasoactive Responses In Vivo

Graepel

Fernandes²,

Aubdool

et al. 2011

J Pharmacol Exp Ther

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“…TRPV1 channels have also been proposed to be involved in the pathogenesis of salt-induced hypertension. TRPV1 expression in mesenteric resistance arteries, the renal cortex and medulla, CGRP levels in dorsal root ganglia, and CGRP-positive sensory nerve density in mesenteric resistance arteries were significantly up-regulated during [57,58] TRPP2 VSMC Contributes to the myogenic response of resistance-size cerebral arteries [47] high-salt intake in Dahl salt-resistant rats, which acted to prevent salt-induced increases in blood pressure [72]. In contrast, TRPV1 expression and function was impaired in Dahl salt-sensitive rats, which rendered Dahl salt-sensitive rats to salt load in terms of blood pressure regulation [72].…”

Section: Trp Channel Subtypes M and V Have Antihypertensive Effectsmentioning

confidence: 97%

“…In a previous study, we demonstrated that TRPM8 activation, by its agonist menthol, antagonized vasoconstriction by inhibiting Ca 2+ signaling-mediated RhoA/ROCK activation in the vasculature [56]. TRPA1 channels are present in the endothelium and mediated vasodilatation via endothelium-dependent and independent mechanisms [57,58]. The role of TRPA1 in the cardiovascular system remains elusive (Table 1).…”

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 Channels and Endothelial Cell Calcium Signaling

Thakore

Earley

2019

Comprehensive Physiology

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The vascular endothelium is a broadly distributed and highly specialized organ. The endothelium has a number of functions including the control of blood vessels diameter through the production and release of potent vasoactive substances or direct electrical communication with underlying smooth muscle cells, regulates the permeability of the vascular barrier, stimulates the formation of new blood vessels, and influences inflammatory and thrombotic processes. Endothelial cells that make up the endothelium express a variety of cell-surface receptors and ion channels on the plasma membrane that are capable of detecting circulating hormones, neurotransmitters, oxygen tension, and shear stress across the vascular wall. Changes in these stimuli activate signaling cascades that initiate an appropriate physiological response. Increases in the global intracellular Ca 2+ concentration and localized Ca 2+ signals that occur within specialized subcellular microdomains are fundamentally important components of many signaling pathways in the endothelium. The transient receptor potential (TRP) channels are a superfamily of cationpermeable ion channels that act as a primary means of increasing cytosolic Ca 2+ in endothelial cells. Consequently, TRP channels are vitally important for the major functions of the endothelium. In this review, we provide an in-depth discussion of Ca 2+-permeable TRP channels in the endothelium and their role in vascular regulation.

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Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo

Abstract: TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders.

Cited by 117 publications

References 38 publications

4-Oxo-2-nonenal (4-ONE): Evidence of Transient Receptor Potential Ankyrin 1-Dependent and -Independent Nociceptive and Vasoactive Responses In Vivo

4-Oxo-2-nonenal (4-ONE): Evidence of Transient Receptor Potential Ankyrin 1-Dependent and -Independent Nociceptive and Vasoactive Responses In Vivo

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

Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

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