5-HYDROXYTRYPTAMINE MEDIATES ENDOTHELIUM DEPENDENT CORONARY VASODILATATION IN THE ISOLATED RAT-HEART BY THE RELEASE OF NITRIC-OXIDE

被引:39
|
作者
MANKAD, PS [1 ]
CHESTER, AH [1 ]
YACOUB, MH [1 ]
机构
[1] NATL HEART & LUNG INST,LONDON SW3,ENGLAND
关键词
5-HT; RAT HEART; ENDOTHELIUM; NITRIC OXIDE; EDRF; VASODILATATION;
D O I
10.1093/cvr/25.3.244
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Study objective - The aim was to investigate further the endothelium dependent vasodilator action of 5-hydroxytryptamine (5-HT) on the rat coronary circulation. Design - Using saponin to damage the endothelium and L-NMMA (N(G)-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. Experimental material - 56 rat hearts were excised and perfused on a Langendorff preparation. Measurements and main 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-mu-g.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.
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页码:244 / 248
页数:5
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