5-Hydroxytryptamine mediates endothelium dependent coronary vasodilatation in the isolated rat heart by the release of nitric oxide.
OBJECTIVE
The aim was to investigate further the endothelium dependent vasodilator action of 5-hydroxytryptamine (5-HT) on the rat coronary circulation.


METHODS
Using saponin to damage the endothelium and L-NMMA (NG-monomethyl-L-arginine), the selective inhibitor of nitric oxide formation, we examined the role of endothelium and nitric oxide in causing 5-HT induced vasodilatation in the isolated rat heart.


METHODS
56 rat hearts were excised and perfused on a Langendorff preparation.


RESULTS
5-HT at (10(-9) to 10(-5) M) and glyceryl trinitrate at (10(-5) to 10(-3) M) (n = 24) induced a dose dependent increase in coronary flow. Chemical removal of the endothelium by exposure to saponin (30 micrograms.ml-1) (n = 8) abolished the 5-HT induced vasodilatation but had no effect on the response to glyceryl trinitrate. Pretreatment of rats (n = 8) with L-NMMA (100 mg.kg-1) unmasked a strong vasoconstrictor effect of 5-HT but did not affect the glyceryl trinitrate induced vasodilatation. Perfusion of L-NMMA pretreated hearts with L-arginine at 10(-4) M (n = 8) restored the vasodilatation induced by 5-HT but L-arginine perfusion had no effect on the extent of 5-HT or glyceryl trinitrate induced vasodilatation in normal hearts (n = 8).


CONCLUSIONS
In the coronary circulation of the isolated rat heart, 5-HT mediates its vasodilator effect via endothelium dependent release of nitric oxide.
Mankad
P S
PS
National Heart and Lung Institute, London, United Kingdom.
Chester
A H
AH
Yacoub
M H
MH
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D012701:Serotonin