Abstract:
AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce TRPC3 activity and the associated endothelial function, including NO release. METHODS AND RESULTS:Measurements of [Ca(2+)](i) and patch-clamp study in primary cultured porcine coronary endothelial cells, measurements of NO and endothelium-dependent relaxation in porcine coronary arteries, and RT-PCR and western blot were conducted. Pre-treatment with SKF96365 (an inhibitor of TRPCs) or the selective TRPC3 inhibitor Pyr3 significantly decreased bradykinin-induced vasorelaxation. One hour of hypoxia followed by reoxygenation significantly reduced the vasorelaxation (70.3 ± 6.4 vs. 88.9 ± 3.5%) and NO concentration (24.0 ± 1.3 vs. 45.2 ± 2.8 nmol/L), and they were restored by pre-incubation with the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (96.4 ± 1.8% and 41.1 ± 4.7 nmol/L, respectively). In porcine coronary endothelial cells, H-R inhibited bradykinin-activated membrane current (8.6 ± 0.4 vs. 14.0 ± 1.5 pA/pF) and Pyr3-sensitive TRPC3 current (3.8 ± 0.3 vs. 6.3 ± 0.6 pA/pF; P< 0.01). H-R also inhibited bradykinin-induced Ca(2+) influx and the Ca(2+) influx via TRPC3. Cell surface expression of TRPC3 was decreased after H-R. CONCLUSIONS:We have, for the first time, demonstrated that Ca(2+) entry via endothelial TRPC3 contributes to NO release and have revealed that H-R is associated with inhibition of TRPC3 activity. Inhibition of channel trafficking to the cell surface is involved in the underlying mechanism of the decrease of TRPC3 current and the reduction in Ca(2+) entry through TRPC3 during H-R. This study suggests that TRPC3 may have the potential to be a new target for endothelial protection during H-R.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Huang JH,He GW,Xue HM,Yao XQ,Liu XC,Underwood MJ,Yang Qdoi
10.1093/cvr/cvr102subject
Has Abstractpub_date
2011-08-01 00:00:00pages
472-82issue
3eissn
0008-6363issn
1755-3245pii
cvr102journal_volume
91pub_type
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journal_title:Cardiovascular research
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更新日期:1981-06-01 00:00:00
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更新日期:2006-02-01 00:00:00
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更新日期:2011-10-01 00:00:00
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journal_title:Cardiovascular research
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doi:
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更新日期:2004-06-01 00:00:00
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更新日期:1992-04-01 00:00:00
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更新日期:2015-07-01 00:00:00
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更新日期:2001-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2005-10-01 00:00:00
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更新日期:2009-07-15 00:00:00
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更新日期:2003-08-01 00:00:00
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更新日期:2005-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00261-8
更新日期:2000-01-14 00:00:00