Effects of melatonin on rat pial arteriolar diameter in vivo
Effects of melatonin on rat pial arteriolar diameter in vivo
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DOI：
10.1038/sj.bjp.0702714
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发表时间：
1999-08
影响因子：
7.3
通讯作者：
O. Régrigny;P. Delagrange;E. Scalbert;I. Lartaud‐Idjouadiene;J. Atkinson;J. Chillon
中科院分区：
文献类型：
--
作者：
O. Régrigny;P. Delagrange;E. Scalbert;I. Lartaud‐Idjouadiene;J. Atkinson;J. Chillon
根据我们的研究结果，褪黑素降低了大鼠脑血流自动调节的下限，我们以前认为褪黑素收缩脑小动脉。本研究的目的是证明这种血管收缩作用，并研究其机制。使用开放颅骨制备方法，在雄性Wistar大鼠的脑小动脉（30-50 μM）中检查了累积剂量褪黑激素（10 - 10至10 - 6 M）的作用。 大脑小动脉暴露于两个剂量的褪黑激素（3×10− 9和3×10− 8 M），在不存在和存在mt 1和/或MT 2受体拮抗剂luzindole（2×10− 6 M）和Ca 2+激活的K+（BKCa）通道阻滞剂四乙铵（TEA+，10− 4 M）的情况下。在TEA+灌流后检查了L-硝基精氨酸甲酯（L-NAME，10− 8 M）对小动脉的影响。大脑小动脉也暴露于BKCa激活剂NS 1619（10− 5 M）和硝普钠（SNP，10− 8 M），在不存在和存在褪黑激素（3×10− 8 M）的情况下，褪黑激素诱导剂量依赖性收缩，EC 50为3.0±0.1 nM，最大收缩为-15 ± 1%。 Luzindole消除褪黑激素诱导的血管收缩。TEA+诱导显著的血管收缩（−10±2%）。当在TEA+存在下将褪黑激素加入aCSF时，没有观察到额外的血管收缩，而L-NAME仍然诱导血管收缩（−10±1%）。NS 1619诱导的血管舒张（+11.1%）在褪黑激素存在下减少了50%。褪黑激素并未减弱SNP（+12 ± 2%）诱导的血管舒张作用，褪黑激素直接收缩大鼠脑小动脉。这种血管收缩作用是通过在激活MT 1和/或MT 2受体后抑制BKC通道介导的，British Journal of Pharmacology（1999）127，1666-1670; doi：10.1038/sj.bjp.0702714
Based on our finding that melatonin decreased the lower limit of cerebral blood flow autoregulation in rat, we previously suggested that melatonin constricts cerebral arterioles. The goal of this study was to demonstrate this vasoconstrictor action and investigate the mechanisms involved.The effects of cumulative doses of melatonin (10−10to 10−6M) were examined in cerebral arterioles (30–50 μM) of male Wistar rats using an open skull preparation. Cerebral arterioles were exposed to two doses of melatonin (3×10−9and 3×10−8M) in the absence and presence of the mt1and/or MT2receptor antagonist, luzindole (2×10−6M) and the Ca2+‐activated K+(BKCa) channel blocker, tetraethylammonium (TEA+, 10−4M). The effect ofL‐nitro arginine methyl ester (L‐NAME, 10−8M) was examined on arterioles after TEA+superfusion. Cerebral arterioles were also exposed to the BKCaactivator, NS1619 (10−5M), and to sodium nitroprusside (SNP, 10−8M) in the absence and presence of melatonin (3×10−8M).Melatonin induced a dose‐dependent constriction with an EC50of 3.0±0.1 nMand a maximal constriction of −15±1%. Luzindole abolished melatonin‐induced vasoconstriction. TEA+induced significant vasoconstriction (−10±2%). No additional vasoconstriction was observed when melatonin was added to the aCSF in presence of TEA+, whereasL‐NAME still induced vasoconstriction (−10±1%). NS1619 induced vasodilatation (+11±1%) which was 50% less in presence of melatonin. Vasodilatation induced by SNP (+12±2%) was not diminished by melatonin.Melatonin directly constricts small diameter cerebral arterioles in rats. This vasoconstrictor effect is mediated by inhibition of BKCachannels following activation of mt1and/or MT2receptors.British Journal of Pharmacology(1999)127, 1666–1670; doi:10.1038/sj.bjp.0702714