Article date: August 1999
By: Olivier Régrigny, Philippe Delagrange, Elizabeth Scalbert, Isabelle Lartaud‐Idjouadiene, Jeffrey Atkinson, Jean‐Marc Chillon, in Volume 127, Issue 7, pages 1666-1670
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 (10−10 to 10−6 M) 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 (3×10−9 and 3×10−8M) in the absence and presence of the mt1 and/or MT2 receptor antagonist, luzindole (2×10−6M) and the Ca2+‐activated K+ (BKCa) channel blocker, tetraethylammonium (TEA+, 10−4M). The effect of L‐nitro arginine methyl ester (L‐NAME, 10−8M) was examined on arterioles after TEA+ superfusion. Cerebral arterioles were also exposed to the BKCa activator, 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 EC50 of 3.0±0.1 nM and 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+, whereas L‐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 BKCa channels following activation of mt1 and/or MT2 receptors.
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 (10−10 to 10−6 M) 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 (3×10−9 and 3×10−8M) in the absence and presence of the mt1 and/or MT2 receptor antagonist, luzindole (2×10−6M) and the Ca2+‐activated K+ (BKCa) channel blocker, tetraethylammonium (TEA+, 10−4M). The effect of L‐nitro arginine methyl ester (L‐NAME, 10−8M) was examined on arterioles after TEA+ superfusion. Cerebral arterioles were also exposed to the BKCa activator, 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 EC50 of 3.0±0.1 nM and 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+, whereas L‐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 BKCa channels following activation of mt1 and/or MT2 receptors.
British Journal of Pharmacology (1999) 127, 1666–1670; doi:10.1038/sj.bjp.0702714
DOI: 10.1038/sj.bjp.0702714
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