We would like to highlight the further consideration of the nervous system in the mechanistic conclusions of the article "Activation of TRPV1 Dietary Capsaicin Improves Endothelium-Dependent Vaso-relaxation and Prevents Hypertension" (Yang et al., 2010). While the cellular data localizing TRPV1 receptors and demonstrating direct actions of capsaicin on endothelial calcium signals is convincing, the chronic experiments critical for the authors interpretations justify further thoughts. In the first of these experiments, the authors fed rats and mice large amounts of the TRPV1 agonist capsaicin (0.01%-0.02% in chow) for 7 months and found modest reductions in systolic blood pressure in spontaneously hypertensive rats. At these levels of intake, even very conservative estimates (considering bioavailability and blood buffering capacity) of plasma circulating concentrations of capsaicin would reach into the 10-100 nM range. Unfortunately, the initial chronic experiments did not measure plasma levels, but a single dose of gastric capsaicin generated high (10 ng/ml) plasma concentrations lasting more than 1 hr-or a sustained exposure to ~33 nM in plasma. In either case, these pharmacological concentrations of capsaicin may be sufficient to produce excitotoxic changes or widespread, sustained, functional desensitization of TRPV1.
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机译：我们想在文章“ TRPV1膳食辣椒素的活化改善内皮依赖性血管舒张并预防高血压”的机制结论中强调对神经系统的进一步考虑（Yang等，2010）。虽然定位TRPV1受体并证明辣椒素对内皮钙信号具有直接作用的细胞数据令人信服，但对于作者的解释至关重要的长期实验证明了进一步的思考是正确的。在这些实验的第一个实验中，研究人员给大鼠和小鼠喂食了大量TRPV1激动剂辣椒素（食物浓度为0.01％-0.02％）达7个月，发现自发性高血压大鼠的收缩压有所降低。在这些摄入水平下，即使是非常保守的估计（考虑生物利用度和血液缓冲能力），辣椒素的血浆循环浓度也会达到10-100 nM的范围。不幸的是，最初的慢性实验没有测量血浆水平，但是单剂量的辣椒素会产生高浓度（10 ng / ml）的血浆浓度，持续超过1小时或持续暴露于〜33 nM血浆中。无论哪种情况，辣椒素的这些药理学浓度可能足以产生TRPV1的兴奋性毒性变化或广泛，持续的功能性脱敏。
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