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Effect of melatonin in the rat tail artery: role of K + channels and endothelial factors

Effect of melatonin in the rat tail artery: role of K + channels and endothelial factors The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat. Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and α1‐adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation. The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L‐NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium‐intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium‐denuded arteries. While melatonin does not appear to modulate agonist‐induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress. When the Ca2+‐activated K+ channel opener, NS 1619 (10 μM), was present, potentiating effects of melatonin were restored in endothelium‐denuded vessels. However, addition of the opener of ATP‐sensitive K+ channels, cromakalim (3 μM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+‐activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+‐activated K+ channels to produce its potentiating effects. Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+‐activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow‐induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone. British Journal of Pharmacology (1998) 123, 1533–1540; doi:10.1038/sj.bjp.0701761 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Effect of melatonin in the rat tail artery: role of K + channels and endothelial factors

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References (37)

Publisher
Wiley
Copyright
1998 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0701761
pmid
9605558
Publisher site
See Article on Publisher Site

Abstract

The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat. Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and α1‐adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation. The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L‐NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium‐intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium‐denuded arteries. While melatonin does not appear to modulate agonist‐induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress. When the Ca2+‐activated K+ channel opener, NS 1619 (10 μM), was present, potentiating effects of melatonin were restored in endothelium‐denuded vessels. However, addition of the opener of ATP‐sensitive K+ channels, cromakalim (3 μM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+‐activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+‐activated K+ channels to produce its potentiating effects. Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+‐activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow‐induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone. British Journal of Pharmacology (1998) 123, 1533–1540; doi:10.1038/sj.bjp.0701761

Journal

British Journal of Pharmacology – Wiley

Published: Apr 1, 1998

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