Department of Human Physiology, University of Oregon, Eugene, OR 97403-1240, USA.
J Physiol. 2012 Aug 1;590(15):3523-34. doi: 10.1113/jphysiol.2012.236398. Epub 2012 Jun 6.
While it is accepted that NO is responsible for ∼60% of the plateau in cutaneous thermal hyperaemia, a large portion of the response remains unknown. We sought to determine whether the remaining ∼40% could be attributed to EDHF-mediated activation of KCa channels, and whether the epoxyeicosatrienoic acids (EETs), derived via cytochrome P450, were the predominant EDHF active in the response. Four microdialysis fibres were placed in the forearm skin of 20 subjects. In Protocol 1 (n = 10): (1) Control, (2) N(G)-nitro-l-arginine methyl ester (l-NAME), (3) a KCa channel inhibitor, tetraethylammonium (TEA), and (4) TEA + l-NAME. In Protocol 2 (n = 10): (1) Control, (2) l-NAME, (3) a cytochrome P450 inhibitor, sulfaphenazole, and (4) sulfaphenazole + l-NAME. Local heating to 42°C was performed and skin blood flow was measured with laser Doppler flowmetry. Data are presented as the percentage of maximal cutaneous vascular conductance (CVC). All drug sites attenuated plateau CVC from the control site (86 ± 1%) to 79 ± 3% with sulfaphenazole (P = 0.02 from control), 71 ± 3% with TEA (P = 0.01 from control), and further to 38 ± 2% with l-NAME (P < 0.001 from control, P < 0.001 from TEA). Plateau was largely attenuated with sulfaphenazole + l-NAME (24 ± 2%; P = 0.002 from l-NAME), and nearly abolished with l-NAME + TEA (13 ± 2%; P = 0.001 from sulfaphenazole + l-NAME), which was not different from baseline (P = 0.14). Furthermore, the initial peak was just 17 ± 2% with TEA + l-NAME (P < 0.001 from l-NAME). These data suggest EDHFs are responsible for a large portion of initial peak and the remaining 40% of the plateau phase, as administration of TEA in combination with l-NAME abolished the majority of hyperaemia. These data also suggest EETs contribute to about half of the EDHF response.
虽然人们普遍认为,NO 负责约 60%的皮肤热充血的平台期,但仍有很大一部分反应是未知的。我们试图确定剩余的约 40%是否可以归因于 EDHF 介导的 KCa 通道激活,以及来源于细胞色素 P450 的环氧二十碳三烯酸(EETs)是否是该反应中主要的 EDHF 活性物质。将四个微透析纤维放置在 20 名受试者的前臂皮肤中。在方案 1(n = 10)中:(1)对照,(2)N(G)-硝基-L-精氨酸甲酯(L-NAME),(3)KCa 通道抑制剂四乙铵(TEA),和(4)TEA+L-NAME。在方案 2(n = 10)中:(1)对照,(2)L-NAME,(3)细胞色素 P450 抑制剂磺胺酚唑,和(4)磺胺酚唑+L-NAME。局部加热至 42°C,并使用激光多普勒血流仪测量皮肤血流量。数据表示为最大皮肤血管传导率(CVC)的百分比。所有药物部位均使对照部位的平台期 CVC 从 86±1%降至 79±3%(磺胺酚唑与对照相比,P=0.02),从 71±3%降至 38±2%(L-NAME 与对照相比,P<0.001)。磺胺酚唑+L-NAME 使平台期基本衰减(24±2%;与 L-NAME 相比,P=0.002),L-NAME+TEA 使平台期几乎消除(13±2%;与磺胺酚唑+L-NAME 相比,P=0.001),与基线相比无差异(P=0.14)。此外,TEA+L-NAME 时初始峰值仅为 17±2%(与 L-NAME 相比,P<0.001)。这些数据表明,EDHFs 负责初始峰值和平台期的剩余 40%的大部分,因为 TEA 与 L-NAME 联合给药消除了大部分充血。这些数据还表明,EETs 对约一半的 EDHF 反应有贡献。