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Bacterial endotoxin rapidly stimulates prolonged endothelium‐dependent vasodilatation in the rat isolated perfused heart
Author(s) -
Baydoun Anwar R.,
Foale Robert D.,
Mann Giovanni E.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13718.x
Subject(s) - endothelium , vasodilation , medicine , perfusion , pharmacology , cardiology , endocrinology , chemistry
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 n m ). 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 N G ‐nitro‐ l ‐arginine methylester ( l ‐NAME; 50 μ m ) or N G ‐nitro‐ l ‐arginine ( l ‐NOARG; 50 μ m ) blocked the vasodilatation induced by LPS (5 μg ml −1 ). The inhibition caused by these arginine analogues was partially reversed by 1 m m l ‐ but not d ‐arginine. 6 The vasodilator action of LPS was also completely blocked by the glucocorticoid, dexamethasone (10 μ m ) but unaffected by indomethacin (10 μ m ). 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.