Hiett S Christopher, Owen Meredith K, Li Wennan, Chen Xingjuan, Riley Ashley, Noblet Jillian, Flores Sarah, Sturek Michael, Tune Johnathan D, Obukhov Alexander G
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA
Cardiovasc Res. 2014 Sep 1;103(4):607-18. doi: 10.1093/cvr/cvu152. Epub 2014 Jun 15.
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.
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.
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.
瞬时受体电位香草酸亚型1（TRPV1）激动剂辣椒素被认为对心血管健康有益，因为它通过内皮依赖性机制扩张冠状动脉，并可能减缓动脉粥样硬化进展。然而，最近的报告表明，高剂量辣椒素可能会使冠状动脉小动脉收缩，甚至引发心肌梗死。迄今为止，TRPV1激活调节冠状动脉血管张力的机制仍知之甚少。本研究调查了局部作用的血管收缩性促炎激素（自分泌物质）与辣椒素在冠状动脉循环中的作用之间是否存在协同相互作用。
在犬类冠状动脉导管环和分离的平滑肌细胞（CASMCs）中进行实验。等长张力测量显示，单独使用1-10μM辣椒素不会影响冠状动脉环的静息张力。相反，在用Gq/11偶联的FP/TP（前列腺素F/血栓素）受体激动剂前列腺素F2α（PGF2α；10μM）预收缩的内皮完整环中，辣椒素首先诱导短暂扩张，随后是持续收缩。在用PGF2α或血栓素类似物U46619（1μM，一种TP受体激动剂）预收缩的去内皮环中，辣椒素仅诱导持续收缩。TP受体或TRPV1的阻滞剂显著抑制辣椒素的作用，但在存在50μM硝苯地平和70mM氯化钾的情况下仍可观察到这些作用。辣椒素还增强了20mM氯化钾诱导的收缩。CASMCs中的荧光成像实验表明，Gq/11-磷脂酶C（PLC）-蛋白激酶C（PKC）和Ca(2+)-PLC-PKC途径可能参与使CASMC TRPV1通道敏感化。
单独使用辣椒素不会引起犬类冠状动脉导管收缩；然而，用促炎前列腺素-血栓素激动剂预处理可能会揭示辣椒素的血管收缩潜力。
