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Involvement of ATP‐sensitive potassium channels in a model of a delayed vascular hyporeactivity induced by lipopolysaccharide in rats
Author(s) -
Sorrentino Raffaella,
Di Villa Bianca Roberta d'Emmanuele,
Lippolis Laura,
Sorrentino Ludovico,
Autore Giuseppina,
Pinto Aldo
Publication year - 1999
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 - 10.1038/sj.bjp.0702666
Subject(s) - glibenclamide , cromakalim , phenylephrine , potassium channel , potassium channel opener , chemistry , aorta , lipopolysaccharide , medicine , endocrinology , atp sensitive potassium channel , tetraethylammonium , pharmacology , anesthesia , potassium , blood pressure , organic chemistry , diabetes mellitus
We have investigated the role of ATP‐sensitive potassium (K ATP ) channels in an experimental model of a delayed phase of vascular hyporeactivity induced by lipopolysaccharide (LPS) in rats. After 24 h, from LPS treatment, in anaesthetized rats the bolus injection of phenylephrine (PE) produced an increase in mean arterial pressure (MAP) significantly ( P <0.05) reduced in LPS‐treated rats compared to the vehicle‐treated rats. This reduction was prevented by pre‐treatment of rats with glibenclamide (GLB), a selective inhibitor of K ATP channels. GLB administration did not affect the MAP in vehicle‐treated rats but produced an increase of MAP in rats treated with LPS. Cromakalim (CRK), a selective K ATP channel opener, produced a reduction of MAP that was significantly ( P <0.05) higher in LPS‐ than in vehicle‐treated rats. In contrast, the hypotension induced by glyceryl trinitrate (GTN) in LPS‐treated rats was not distinguishable from that produced in vehicle‐treated rats. Experiments in vitro were conducted on aorta rings collected from rats treated with vehicle or LPS 24 h before sacrifice. The concentration‐dependent curve to PE was statistically ( P <0.005) reduced in aorta rings collected from LPS‐ compared to vehicle‐treated rats. This difference was totally abolished by tetraethylammonium (TEA), a non‐selective inhibitor of K + channels. CRK produced a relaxation of PE precontracted aorta rings higher in rings from LPS‐ than in vehicle‐treated rats. GLB inhibited CRK‐induced relaxation in both tissues, abolishing the observed differences. In conclusion, our results indicate an involvement of K ATP channels to the hyporesponsiveness of vascular tissue after 24 h from a single injection of LPS in rats. We can presume an increase in the activity of K ATP channels on vascular smooth muscle cells but we cannot exclude an increase of K ATP channel number probably due to the gene expression activation.British Journal of Pharmacology (1999) 127 , 1447–1453; doi: 10.1038/sj.bjp.0702666