CEREBROVASCULAR RESPONSES TO CAPSAICIN INVITRO AND INSITU
CEREBROVASCULAR RESPONSES TO CAPSAICIN INVITRO AND INSITU
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DOI：
10.1111/j.1476-5381.1990.tb15801.x
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发表时间：
1990-06-01
影响因子：
7.3
通讯作者：
MCCULLOCH, J
中科院分区：
文献类型：
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作者：
EDVINSSON, L;JANSEN, I;MCCULLOCH, J
1.本实验观察了辣椒素对猫离体脑动脉(长2-3 mm，外径300-400微米)和软脑膜小动脉(外径40-200微米)的影响。2.在分离的大脑中动脉上，低浓度辣椒素(10~(-14)~10~(-10)M)对前列腺素F_(2α)预收缩的血管具有浓度依赖性的松弛作用。重复使用辣椒素可显著减弱这种松弛反应，但阿托品、心得安、西咪替丁或Spantide的存在对松弛反应的影响很小。3.在分离的大脑中动脉上，较高浓度的辣椒素可引起明显的浓度依赖性收缩。这种收缩不被10-6M酚妥拉明或10-6M酮丝氨酸所改变。从缓冲溶液中去除钙离子后，辣椒素的收缩作用明显减弱。钙通道阻滞剂尼莫地平也逆转了辣椒素引起的收缩。4.蛛网膜下腔血管周围原位微量注射辣椒素可引起双相反应(先收缩血管后持续扩张)。最大血管收缩指数为60。+-。直径较基线缩小6%，最大血管扩张为38.+-。直径增加了7%。血管扩张发生在较低浓度的辣椒素(EC50)，约5倍。10-8M)，比血管收缩所需EC50(EC50)高3倍。10-7M)。5.三叉神经节切除前10~16天，阻断血管周围应用辣椒素(10~(-6)M)的血管扩张作用，但对该药的血管收缩作用无影响。6.在同一小动脉周围重复注射辣椒素(10~(-6)M)可使反应的血管扩张相逐渐减弱，但不改变血管收缩相。7.本研究提示辣椒素引起的脑血管扩张是由于脑血管三叉神经纤维释放血管活性物质所致，而辣椒素的血管收缩作用是通过细胞外钙跨膜通道直接作用于脑血管的。
1. The cerebrovascular effects of capsaicin have been examined in vitro, in feline isolated cerebral arteries (circular segments, 2-3 mm long, 300-400.mu.m extended diameter) and, in situ, in pial arterioles (diameter 40-200.mu.m) on the cortical surface of chloralose-anaesthetized rats. 2. In isolated middle cerebral arteries, low concentrations of capsaicin (10-14-10-10M) effected a concentration-dependent relaxation of vessels precontracted with prostaglandin F2.alpha.. This relaxant response was markedly attenuated by repeated administration of capsaicin but was minimally affected by the presence of atropine, propranolol, cimetidine or spantide in the tissue bath. 3. In isolated middle cerebral arteries, higher concentrations of capsaicin effected a marked concentration-dependent contraction. This contraction was not modified by 10-6M phentolamine or 10-6M ketanserin. A markedly reduced contraction by capsaicin was found upon the removal of calcium ions from the buffer solution. Also the calcium entry blocker nimodipine reversed the capsaicin-induced contraction. 4. Subarachnoid perivascular microapplication of capsaicin around individual pial arterioles in situ elicited a biphasic response (an immediate vasoconstriction followed by a sustained vasodilatation). The maximum vasoconstriction was a 60 .+-. 6% reduction in diameter from base line and the maximum vasodilatation a 38 .+-. 7% increase in diameter. Vasodilatation occurred at lower concentrations of capsaicin (EC50, approximately 5 .times. 10-8M) than those required for vasoconstriction (EC50 3 .times. 10-7M). 5. Trigeminal ganglionectomy 10-16 days before the microapplication abolished the in situ vasodilator effects of capsaicin (10-6M) applied perivascularly, but was without effect on the vasoconstrictor actions of this agent. 6. Repeated administration of capsaicin (10-6M) around the same arteriole resulted in a progressive attenuation of the vasodilator phase of the response, with no modification of the vasoconstrictor phase. 7. The present study suggests that capsaicin-induced cerebral vasodilatation is due to the release of vasoactive agents from cerebrovascular trigeminal nerve fibres, whereas the vasoconstrictor effect of capsaicin is due to a direct effect on the cerebral vasculature which is mediated via the transmembrane passage of extracellular calcium.