Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm

作者：Hiett S Christopher; Owen Meredith K; Li Wennan; Chen Xingjuan; Riley Ashley; Noblet Jillian; Flores Sarah; Sturek Michael; Tune Johnathan D; Obukhov Alexander G^*

来源：Cardiovascular Research, 2014, 103(4): 607-618.

DOI：10.1093/cvr/cvu152

• TRPV1
• Coronary artery
• Pro-inflammatory prostaglandin-thromboxane hormones

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 mu M capsaicin alone did not affect resting tension of coronary artery rings. In contrast, in endothelium-intact rings pre-contracted with a G(q/11)-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F-2 alpha (PGF(2 alpha); 10 mu M), capsaicin first induced transient dilation that was followed by sustained contraction. In endothelium-denuded rings pre-contracted with PGF2a or thromboxane analogue U46619 (1 mu M, 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 mM nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that the G(q/11)-phospholipase C (PLC)-protein kinaseC(PKC) and Ca2+-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.

• 出版日期2014-9-1