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Investigation of the functional role of TRPC3 and TRPV4 in endothelium-dependent modulation of tone in rat mesenteric arteries
Abstract   Peer reviewed

Investigation of the functional role of TRPC3 and TRPV4 in endothelium-dependent modulation of tone in rat mesenteric arteries

R Wei, S E Lunn, Shaun L Sandow, T V Murphy, P M Kerr and F Plane
Microcirculation, pp.67-68
World Congress for Microcirculation, 10th (Kyoto, Japan, 25-Sep-2015–27-Sep-2015)
2015
DOI: https://doi.org/10.1111/micc.12246
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https://doi.org/10.1111/micc.12246View
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Abstract

Medical and Health Sciences
Transient receptor potential (TRP) channels contribute to endothelial cytosolic calcium signaling. Roles for both transient receptor potential C3 (TRPC3) and vallinoid type4 (TRPV4) in agonist-evoked endothelium-dependent vascular relaxation have been proposed. Thus, in this study we have investigated the functional contribution of these channels to endothelium-dependent modulation of phenylephrine- and nerve-evoked increases in tone and to acetylcholine-evoked relaxation in rat mesenteric arteries. Using an immunohistochemical approach, TRPC3 and TRPV4 antibodies showed low level diffuse and punctate labeling in endothelial cells and absence in smooth muscle cells. 1-[4- [(2,3,3-Trichloro-1-oxo-2-propen-1-yl)amino]phenyl]-5- (trifluoromethyl)-1H-pyrazole-4-carboxylic acid (Pyr3), a selective inhibitor of TRPC3 channels enhanced nerve- and phenylephrine-induced increases in tone in endotheliumintact arteries but was without effect on acetylcholine-evoked relaxations. 1-(4-chloro-2-nitrophenyl) sulfonyl-4-benzylpiperazine (RN 1747), an agonist at TRPV4 channels, did not alter vascular tone when applied alone but did enhance endothelium-dependent relaxations to acetylcholine, an effect which was blocked by 3-([1,40 -bipiperidin]-10 -ylmethyl)-7-bromo-N- (1-phenylcyclopropyl)- 2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK 2193874) a selective inhibitor of TRPV4 channels. However, GSK 2193874 alone did not alter nerve- of phenylephrine-induced responses or acetylcholine-evoked relaxations. Our findings indicate that TRPC3 channels are involved in endothelium-dependent modulation of smooth muscle contraction but do not appear to contribute to acetylcholine-evoked vasorelaxation. In contrast, inhibition of TRPV4 channels does not appear to alter vascular tone but activation of these channels does enhance vasorelaxation to acetylcholine. Thus, despite showing a similar pattern of endothelial localization, TRPC3 and TRPV4 make distinct contributions to regulation of arterial diameter in rat mesenteric arteries.Supported by HSFC and FoMD 75th Anniversary Award.

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