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. 1993 Aug;109(4):987–991. doi: 10.1111/j.1476-5381.1993.tb13718.x

Bacterial endotoxin rapidly stimulates prolonged endothelium-dependent vasodilatation in the rat isolated perfused heart.

A R Baydoun 1, R D Foale 1, G E Mann 1
PMCID: PMC2175763  PMID: 8401952

Abstract

1. The effects of bacterial lipopolysaccharide (Escherichia coli 0111-B4; LPS) on coronary vascular tone were examined in the isolated perfused heart of the rat. The role of nitric oxide and/or prostaglandin products of the cyclo-oxygenase pathway in mediating the actions of LPS were also investigated. 2. Coronary vascular tone was raised and maintained by a continuous perfusion of the thromboxane-mimetic U46619 (5 nM). LPS perfusion (0.1-100 micrograms ml-1) caused a concentration-dependent fall in coronary tone without any significant change in the force of cardiac contractility. 3. At 5 micrograms ml-1, LPS reduced perfusion pressure by 38 +/- 9 mmHg. This effect was rapid in onset, maximal within the first 5 min and sustained for 90 +/- 10 min (n = 6). 4. The vasodilatation induced by LPS was dependent on the presence of an intact endothelium and abolished following endothelial damage caused by air embolism. 5. NG-nitro-L-arginine methylester (L-NAME; 50 microM) or NG-nitro-L-arginine (L-NOARG; 50 microM) blocked the vasodilatation induced by LPS (5 micrograms ml-1). The inhibition caused by these arginine analogues was partially reversed by 1 mM L- but not D-arginine. 6. The vasodilator action of LPS was also completely blocked by the glucocorticoid, dexamethasone (10 microM) but unaffected by indomethacin (10 microM). 7. These results suggest that LPS evokes rapid release of nitric oxide (NO) in the microvasculature of the rat isolated heart presumably via activation of the constitutive L-arginine-NO pathway in the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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