Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel
Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel
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DOI：
10.1161/circresaha.107.154443
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发表时间：
2007-07-20
影响因子：
20.1
通讯作者：
Heurteaux, Catherine
中科院分区：
文献类型：
--
作者：
Blondeau, Nicolas;Petrault, Olivier;Heurteaux, Catherine
血管闭塞是导致神经元损伤的脑内局部血流受损的最常见原因，并且是全世界残疾和死亡的主要原因。多不饱和脂肪酸，特别是α-亚麻酸，可提高脑对脑缺血的抵抗力。本研究的目的是评估多不饱和脂肪酸，特别是α-亚麻酸对脑血流量和调节脑灌注的血管张力的影响。α-亚麻酸注射增加脑血流量并诱导基底动脉而不是颈动脉的血管舒张。饱和脂肪酸棕榈酸不产生血管舒张作用。这表明多不饱和脂肪酸作用的靶点是TREK-1钾通道。我们证明了这个通道存在于基底动脉，但不是在颈动脉。我们发现，在TREK-1（-/-）小鼠中，基底动脉中多不饱和脂肪酸诱导的血管舒张以及激光多普勒血流增加被取消。总之，这些数据表明，TREK-1激活引起了强烈的扩张，这可能是由多不饱和脂肪酸如α-亚麻酸或二十二碳六烯酸诱导的脑血流量增加的原因。他们认为，脑侧支中TREK-1的选择性表达和激活可能在多不饱和脂肪酸通过在缺血期间提供残余循环来对抗中风的保护机制中发挥重要作用。
Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.