Role of Transient Receptor Potential Canonical 5 (TRPC5) Channels in Vascular Tone Regulation
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AbstractIntracellular Ca2+ concentration in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) plays an important role in vascular tone control and blood pressure regulation. Previously, most research focused on voltage-dependent Ca2+ channels which mediate Ca2+ influx and vascular contraction. However, recent focus has been shifted to TRP channels. Reports show that several TRP channels, including TRPC1 and TRPC3, have important regulatory role in vascular tone control. However, there are relatively few studies about the role of TRPC5 channels in vascular tone regulation.
In present study, we determined the expression of TRPC5 in mouse carotid arteries, aorta and mesenteric arteries. Immunohistochemical staining results demonstrated that TRPC5 is expressed in both ECs and VSMCs. Consistently, Western blot results also showed TRPC5 expression. Isometric tension of arteries was measured using wire myograph. In carotid arteries, selective TRPC5 inhibitor clemizole attenuated endothelium-dependent contraction (EDC) in a dose-dependent manner; another TRPC5 inhibitor ML204 also dramatically inhibited EDC. Importantly, EDC in carotid arteries from TRPC5 knockout (KO) mice was substantially lower compared with that of wild type (WT) mice. These results indicate that TRPC5 contributes to EDC response in mouse carotid arteries. Attempts were made to determine which cyclooxygenase (COX) mediates EDC in carotid arteries. In both TRPC5 WT and KO mice, selective COX-2 inhibitor NS-398 dramatically reduced EDC, while selective COX-1 inhibitor VAS only slightly inhibited it. Non-selective COX inhibitor indomethacin abolished EDC. Similar studies were performed using small mesenteric arteries. We found that ANG II-induced contraction in KO mice was lower than in WT mice. This difference disappeared after removal of endothelium layer. Furthermore, clemizole significantly inhibited ANG II-induced contraction. Taken together, our studies suggest that TRPC5 contributes to EDC response in mouse carotid arteries, and it also plays a role in ANG II-induced contraction in mouse small mesenteric arteries.
All Author(s) ListLiang C, Yao XQ
Name of ConferenceASPET 2017 Annual Meeting at Experimental Biology
Start Date of Conference22/04/2017
End Date of Conference26/04/2017
Place of ConferenceChicago
Country/Region of ConferenceUnited States of America
Year2017
LanguagesEnglish-United States

Last updated on 2018-22-01 at 09:20