Migraine can be induced by sildenafil without changes in middle cerebral artery diameter
Migraine can be induced by sildenafil without changes in middle cerebral artery diameter
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DOI：
10.1093/brain/awg009
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发表时间：
2003-01-01
期刊：
影响因子：
14.5
通讯作者：
Olesen, J
中科院分区：
文献类型：
--
作者：
Kruuse, C;Thomsen, LL;Olesen, J
偏头痛被认为是一种涉及脑动脉扩张的神经血管疾病。一氧化氮(NO)供体可引起脑动脉和颅外动脉扩张及偏头痛，但除了其环状鸟苷(CGMP)介导的血管扩张外，NO还有几种作用机制。我们研究了西地那非(伟哥(R))，一种选择性的cGMP水解型磷酸二酯酶5(PDE5)的抑制剂，它只通过增加cGMP起作用，是否可以引起偏头痛和脑动脉扩张。在这项双盲、安慰剂对照的交叉研究中，我们纳入了12名没有先兆的偏头痛患者，其中安慰剂或西地那非100 mg分别在两天内口服。经颅多普勒超声检测大脑中动脉血流速度(V-MCA)，单光子发射计算机断层扫描(SPECT)和氙气吸入法测定大脑中动脉局部血流量(RCBF)。用高频超声研究了桡动脉和颞动脉的内径。重复测定头痛反应、颅周肌肉压痛、血压和心率。我们发现，在12名偏头痛患者中，有10名患者的偏头痛发作是由西地那非引起的，而在12名患者中，有2名患者是由安慰剂引起的(P=0.01)。西地那非治疗后，v-MCA(P=0.1)和rCBF(P=0.93)无明显变化。西地那非对颞动脉(P=0.47)和桡动脉(P=0.87)的管径和颅周压痛(P=0.16)无影响。西地那非治疗后，收缩压和舒张压无明显变化，但心率从平均62+/-2次/分增加到74+/-3次/分(P=0.01)。我们的结果表明，偏头痛可能是通过cGMP依赖的机制诱导的，而且我们首次证明，这种情况发生时大脑中动脉没有最初的扩张。我们认为，触发机制可能存在于血管周围感觉神经末梢或脑干。然而，其他作用部位也是可能的，还需要进一步的研究来阐明这一点。在临床使用西地那非时，应告知偏头痛患者偏头痛发作的风险。
Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra(R)), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V-mca) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBF(mca)) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P=0.01). V-mca (P=0.1) and rCBF(mca) (P=0.93) remained unchanged after sildenafil. Temporal (P=0.47) and radial (P=0.87) artery diameter and pericranial tenderness (P=0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62+/-2 to 74+/-3 beats/min (P=0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.