Abstract:
AIMS:The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may constrict coronary arterioles and even provoke myocardial infarction. Thus far, the mechanisms by which TRPV1 activation modulates coronary vascular tone remain poorly understood. This investigation examined whether there is a synergistic interplay between locally acting vasoconstrictive pro-inflammatory hormones (autacoids) and capsaicin effects in the coronary circulation. METHODS AND RESULTS:Experiments were performed in canine conduit coronary artery rings and isolated smooth muscle cells (CASMCs). Isometric tension measurements revealed that 1-10 μM capsaicin alone did not affect resting tension of coronary artery rings. In contrast, in endothelium-intact rings pre-contracted with a Gq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation that was followed by sustained contraction. In endothelium-denuded rings pre-contracted with PGF2α or thromboxane analogue U46619 (1 μM, a TP receptor agonist), capsaicin induced only sustained contraction. Blockers of the TP receptor or TRPV1 significantly inhibited capsaicin effects, but these were still observed in the presence of 50 μM nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that the Gq/11-phospholipase C (PLC)-protein kinase C (PKC) and Ca(2+)-PLC-PKC pathways are likely involved in sensitizing CASMC TRPV1 channels. CONCLUSION:Capsaicin alone does not cause contractions in conduit canine coronary artery; however, pre-treatment with pro-inflammatory prostaglandin-thromboxane agonists may unmask capsaicin's vasoconstrictive potential.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Hiett SC,Owen MK,Li W,Chen X,Riley A,Noblet J,Flores S,Sturek M,Tune JD,Obukhov AGdoi
10.1093/cvr/cvu152subject
Has Abstractpub_date
2014-09-01 00:00:00pages
607-18issue
4eissn
0008-6363issn
1755-3245pii
cvu152journal_volume
103pub_type
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更新日期:2003-10-01 00:00:00
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更新日期:1997-02-01 00:00:00
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doi:10.1016/j.cardiores.2005.11.020
更新日期:2006-03-01 00:00:00
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更新日期:2013-07-01 00:00:00
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doi:10.1093/cvr/cvn355
更新日期:2009-03-01 00:00:00
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更新日期:2002-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.026
更新日期:2007-12-01 00:00:00
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更新日期:2003-03-15 00:00:00
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更新日期:2014-07-01 00:00:00