Direct biochemical evidence for eNOS stimulation by bradykinin in the human forearm vasculature
Direct biochemical evidence for eNOS stimulation by bradykinin in the human forearm vasculature
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DOI：
10.1007/s003950300000
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发表时间：
2003-03-01
影响因子：
9.5
通讯作者：
Kelm, M
中科院分区：
文献类型：
--
作者：
Lauer, T;Kleinbongard, P;Kelm, M
目的虽然最近研究表明乙酰胆碱（ACh）引起的前臂阻力血管舒张主要由一氧化氮（NO）介导，但缓激肽（BK）刺激人动脉循环中内皮型一氧化氮合酶（eNOS）活性的直接生化证据仍缺乏。因此，本研究的目的是测试的假设，在人前臂血管eNOS刺激显着有助于BK诱导的血管舒张。方法16名健康志愿者，在有和无NOS抑制剂L-NMMA（8 μ mol/min）的情况下，肱动脉灌注BK，并与乙酰胆碱灌注后的毒蕈碱能eNOS刺激进行比较。前臂血流量（FBF）测定静脉闭塞体积描记术，血浆亚硝酸盐（NO2-），这是一个敏感和特异性的区域eNOS活性的标志物，测定在肘前静脉和肱动脉流动注射分析。一氧化氮的产生计算为NO2浓度的静脉-动脉差异乘以FBF的乘积。结果：20，60，200 ng/min）以及毒蕈碱能（ACh：1，3，10 μ g/min）刺激导致每个个体的FBF和NO2-呈剂量依赖性增加。BK输注后FBF与NO产生的关系与ACh相当（r = 0.98; n = 64，p < 0.01）。此外，NOS抑制降低了流动反应和NO的产生（BK：54和75%; ACh：57和72%），以类似的程度。结论eNOS参与缓激肽引起的人前臂阻力血管舒张反应。
Objective Although it has been shown recently that acetylcholine (ACh)-induced vasodilation of forearm resistance vessels is predominantly mediated by nitric oxide, direct biochemical evidence for eNOS stimulation by bradykinin (BK) in the human arterial circulation is still lacking. Therefore, the present study was designed to test the hypothesis that in the human forearm vasculature eNOS stimulation significantly contributes to BK-induced vasodilation. Methods BK was infused in the presence and absence of the NOS inhibitor L-NMMA (8 mumol/min) into the brachial artery of 16 healthy volunteers and the effects compared to muscarinergic eNOS stimulation following acetylcholine infusion. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and plasma nitrite (NO2-), which represents a sensitive and specific marker of regional eNOS activity, was determined in the antecubital vein and brachial artery by flow injection analysis. Nitric oxide production was calculated as product of the veno-arterial difference of NO2- concentration times FBF. Results Kininergic (BK: 20, 60, 200 ng/min) as well as muscarinergic (ACh: 1, 3, 10 mug/min) stimulation resulted in a dose-dependent increase in FBF and NO2- in each individual. The relationship between FBF and NO production upon BK infusion was comparable to that obtained with ACh (r = 0.98; n = 64, p < 0.01). Moreover, NOS inhibition reduced both flow responses and NO production (BK: 54 and 75 %; ACh: 57 and 72 %) to a similar extent. Conclusions These data provide direct biochemical evidence for the involvement of eNOS in bradykinin-induced vasodilation of forearm resistance vessels in humans.