Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania, USA.
Am J Hypertens. 2017 Nov 6;30(12):1156-1162. doi: 10.1093/ajh/hpx127.
Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal.
Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer's (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax).
At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups.
Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.
薄荷醇是一种选择性瞬时受体电位 melastatin 8（TRPM8）通道激动剂，可通过一氧化氮合酶（NOS）、内皮衍生超极化因子（EDHF）和感觉神经介导的机制诱导年轻、血压正常的男性和女性皮肤血管扩张。原发性高血压存在微血管功能障碍，薄荷醇是否诱导血管扩张在男性和女性原发性高血压患者中尚无定论。
在 9 名原发性高血压患者和 10 名年龄匹配的正常血压对照者的前臂放置 4 个真皮内微透析纤维。部位用乳酸林格氏液（对照）、l-NAME（NOS 抑制）、TEA（EDHF 抑制）和利多卡因（感觉神经抑制）预处理。然后用 7 种递增剂量的薄荷醇（0.1-500 mM）灌注微透析纤维。用激光多普勒血流仪测量薄荷醇引起的红细胞通量。数据归一化为平均动脉压，并表示为特定部位最大血管扩张的百分比（%CVCmax）。
在对照部位，薄荷醇引起正常血压组和高血压组的血管扩张（薄荷醇剂量 100、250 和 500 mM；与基线相比，所有 P<0.05）。两组之间无差异（P=0.58，主要效应）。NOS 或感觉神经抑制对正常血压组薄荷醇诱导的血管扩张均无影响；然而，NOS 和感觉神经抑制可减弱高血压组薄荷醇诱导的血管扩张。EDHF 抑制可减弱两组薄荷醇诱导的血管扩张。
薄荷醇诱导的血管扩张具有 NO、EDHF 和感觉神经成分。薄荷醇诱导的皮肤血管扩张在高血压患者中得到保留。然而，高血压患者表现出冗余血管扩张系统的丧失。
