TY - JOUR
T1 - Mechanisms underlying capsaicin effects in canine coronary artery
T2 - Implications for coronary spasm
AU - Hiett, S. Christopher
AU - Owen, Meredith K.
AU - Li, Wennan
AU - Chen, Xingjuan
AU - Riley, Ashley
AU - Noblet, Jillian
AU - Flores, Sarah
AU - Sturek, Michael
AU - Tune, Johnathan D.
AU - Obukhov, Alexander G.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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 aGq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation thatwas 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 μM KCl. Capsaicin also potentiated 20 μM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that theGq/11-phospholipaseC(PLC)-protein kinaseC(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.
AB - 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 aGq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation thatwas 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 μM KCl. Capsaicin also potentiated 20 μM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that theGq/11-phospholipaseC(PLC)-protein kinaseC(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.
KW - Coronary artery
KW - Pro-inflammatory prostaglandin-thromboxane hormones
KW - TRPV1
UR - http://www.scopus.com/inward/record.url?scp=84907354543&partnerID=8YFLogxK
U2 - 10.1093/cvr/cvu152
DO - 10.1093/cvr/cvu152
M3 - Article
C2 - 24935430
AN - SCOPUS:84907354543
SN - 0008-6363
VL - 103
SP - 607
EP - 618
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 4
ER -