Glyceryl trinitrate may trigger endogenous nitric oxide production in patients with chronic tension-type headache
Glyceryl trinitrate may trigger endogenous nitric oxide production in patients with chronic tension-type headache
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DOI：
10.1111/j.1468-2982.2004.00780.x
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发表时间：
2004-11-01
期刊：
影响因子：
4.9
通讯作者：
Olesen, J
中科院分区：
文献类型：
--
作者：
Ashina, M;Simonsen, H;Olesen, J
人体实验研究表明，一氧化氮（NO）可能在原发性头痛的发病中起重要作用。有人提出，l -精氨酸-NO途径的激活和内源性NO生成的增加可能是NO诱导头痛的原因。一氧化氮是由l -精氨酸合成的，该反应也产生瓜氨酸。在本研究中，我们旨在研究血浆中瓜氨酸和精氨酸水平作为一氧化氮供体三硝酸甘油（GTN）输注后一氧化氮产生的标志物。我们招募了16名慢性紧张性头痛患者和16名健康对照者。受试者被随机分配在20分钟内接受0.5杯/千克/分钟的GTN或安慰剂。患者在无头痛日接受检查。在基线和开始输注后60分钟采集血样。与安慰剂组相比，患者和对照组在GTN组当天出现了更强烈的即时头痛（P = 0.008）。患者的头痛比对照组更明显（P = 0.02）。与安慰剂输注相比，GTN输注后60分钟患者血浆瓜氨酸水平显著升高（P = 0.01），而对照组无显著升高（P = 0.50）。两组患者血浆精氨酸水平（P = 0.12）和对照组（P = 0.18）均无变化。我们认为GTN给药可能触发慢性紧张性头痛患者内源性NO的产生，导致血管周围感觉传入神经的激活。
Experimental studies in humans have shown that nitric oxide (NO) may play an important role in initiation of primary headaches. It has been proposed that activation of L-arginine-NO pathway and increased endogenous production of NO may be responsible for NO induced headache. NO is synthesized from L-arginine and that reaction also yields citrulline. In the present study we aimed to investigate plasma levels of citrulline and arginine as markers of NO production after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 mug/kg/min GTN or placebo over 20 min. Patients were examined on headache free days. Blood samples were collected at baseline and 60 min after start of infusion. Both patients and controls developed stronger immediate headache on the GTN day than on the placebo day (P = 0.008). The headache was more pronounced in patients than in controls (P = 0.02). Plasma levels of citrulline increased significantly 60 min after start of GTN infusion compared to placebo infusion in patients (P = 0.01) but not in controls (P = 0.50). Plasma levels of arginine were unchanged in both patients (P = 0.12) and controls (P = 0.18). We suggest that GTN administration may trigger endogenous production of NO in patients with chronic tension-type headache resulting in activation of perivascular sensory afferents.