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

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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 μg ml−1) caused a concentration-dependent fall in coronary tone without any significant change in the force of cardiac contractility. 3 At 5 μg 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 μm) or NG-nitro-l-arginine (l-NOARG; 50 μm) blocked the vasodilatation induced by LPS (5 μg 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 μm) but unaffected by indomethacin (10 μm). 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. Furthermore, the lack of effect of indomethacin suggests that prostaglandins released via the cyclo-oxygenase pathway are not involved in mediating this action of LPS.

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