Vol. 280, Issue 1, H76-H82, January 2001
Melatonin potentiates contractile responses to serotonin in
isolated porcine coronary arteries
Qiong
Yang1,
Elizabeth
Scalbert2,
Philippe
Delagrange2,
Paul M.
Vanhoutte2, and
Stephen T.
O'Rourke1
1 Department of Pharmaceutical Sciences, North Dakota State
University, Fargo, North Dakota 58105; and 2 Institut de
Recherches Internationales Servier, 92415 Courbevoie Cedex,
France
The present study was designed to
determine the effects of melatonin on coronary vasomotor tone. Porcine
coronary arteries were suspended in organ chambers for isometric
tension recording. Melatonin (10
10-105 M)
itself caused neither contraction nor relaxation of the tissues. Serotonin (109-105 M) caused
concentration-dependent contractions of coronary arteries, and in the
presence of melatonin (107 M) the maximal response to
serotonin was increased in rings with but not without endothelium. In
contrast, melatonin had no effect on contractions produced by the
thromboxane A2 analog U-46619 (1010-107 M). The melatonin-receptor
antagonist S-20928 (106 M) abolished the potentiating
effect of melatonin on serotonin-induced contractions in
endothelium-intact coronary arteries, as did treatment with
1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (105 M),
methylene blue (105 M), or
NG-nitro-L-arginine (3 × 105 M). In tissues contracted with U-46619, serotonin
caused endothelium-dependent relaxations that were inhibited by
melatonin (107 M). Melatonin also inhibited coronary
artery relaxation induced by sodium nitroprusside
(109-105 M) but not by isoproterenol
(109-105 M). These results support the
hypothesis that melatonin, by inhibiting the action of nitric oxide on
coronary vascular smooth muscle, selectively potentiates the
vasoconstrictor response to serotonin in coronary arteries with endothelium.
nitric oxide; sodium nitroprusside; vasoconstriction; vascular
smooth muscle
