The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans
The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans
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DOI：
10.1152/japplphysiol.90412.2008
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发表时间：
2008-07-01
影响因子：
3.3
通讯作者：
Johnson, John M.
中科院分区：
文献类型：
--
作者：
Hodges, Gary J.;Kosiba, Wojciech A.;Johnson, John M.
突触前阻断皮肤血管收缩神经（VCN）可消除缓慢局部加热（SLH）过程中的轴突反射（AR），并降低血管舒张反应。在两部分研究中，前臂部位装有微透析纤维、局部加热器和激光多普勒血流探头。在第1部分中，我们测试了VCN的这种作用是否通过一氧化氮合酶（NOS）起作用。在5名受试者中，治疗如下：1）未治疗; 2）溴苄铵，防止神经递质释放; 3）N-G-硝基-L-精氨酸甲酯（L-NAME），抑制NOS;和4）组合溴苄铵+ L-NAME。在治疗部位，AR消失，最终血管舒张功能减弱（P < 0.05），不同部位之间无差异（P > 0.05）。在第2部分，我们测试是否去甲肾上腺素和/或神经肽Y参与皮肤血管扩张反应SLH。在7例受试者中，治疗如下：1）未治疗; 2）普萘洛尔和育亨宾拮抗α和β受体; 3）BIBF-3226拮抗Y-1受体; 4）普萘洛尔+育亨宾+BIBF-3226联合治疗。普萘洛尔+育亨宾或BIBF-3226治疗显著升高AR发生时的温度（n = 4）或消除AR（n = 3）。重要的是，SLH治疗部位的最终血管舒张作用显著低于对照组（P < 0.05）。这些数据表明，去甲肾上腺素和神经肽Y是重要的启动AR和实现一个完整的血管扩张反应。由于VCN和NOS阻断剂联合使用的抑制作用并不比单独使用时大，因此这些数据表明VCN通过一氧化氮依赖性机制促进热诱导的血管舒张。
Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40 C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) N-G-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS; and 4) combined bretylium + L-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation (P < 0.05), which was not different among those sites (P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize alpha- and beta-receptors; 3) BIBP-3226 to antagonize Y-1 receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred (n = 4) or abolished it (n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly (P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.