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.
10th World Congress for Microcirculation, Kyoto, Japan 25-27 September 2015