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Dexamethasone improves vascular hyporeactivity induced by LPS in vivo by modulating ATP‐sensitive potassium channels activity
Author(s) -
D'Emmanuele Di Villa Bianca R,
Lippolis L,
Autore G,
Popolo A,
Marzocco S,
Sorrentino L,
Pinto A,
Sorrentino R
Publication year - 2003
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.0705406
Subject(s) - phenylephrine , dexamethasone , cromakalim , potassium channel , in vivo , lipopolysaccharide , medicine , endocrinology , pharmacology , glucocorticoid , antagonist , potassium channel opener , chemistry , receptor , agonist , biology , microbiology and biotechnology , blood pressure
Septic shock represents an important risk factor for patients critically ill. This pathology has been largely demonstrated to be a result of a myriad of events. Glucocorticoids represent the main pharmacological therapy used in this pathology. Previously we showed that ATP‐sensitive potassium (K ATP ) channels are involved in delayed vascular hyporeactivity in rats (24 h after Escherichia coli lipopolysaccharide (LPS) injection). In LPS‐treated rats, we observed a significant hyporeactivity to phenylephrine (PE) that was reverted by glybenclamide (GLB), and a significant increase in cromakalim (CRK)‐induced hypotension. We evaluated the effect of dexamethasone (DEX 8 mg kg −1 i.p.) whether on hyporeactivity to PE or on hyperreactivity to CRK administration, in vivo , in a model of LPS (8 × 10 6 U kg −1 i.p.)‐induced endotoxemia in urethane‐anaesthetised rats. DEX treatment significantly reduced, in a time‐dependent manner, the increased hypotensive effect induced by CRK in LPS‐treated rats. This effect was significantly ( P <0.05) reverted by the glucocorticoid receptor antagonist RU38486 (6.6 mg kg −1 i.p.). GLB‐induced hypertension (40 mg kg −1 i.p.), in LPS‐treated rats, was significantly inhibited by DEX if administered at the same time of LPS. Simultaneous administration of DEX and LPS to rats completely abolished the hyporeactivity to PE observed after 24 h from LPS injection. In conclusion, our results suggest that the beneficial effect of DEX in endotoxemia could be ascribed, at least in part, to its ability to interfere with K ATP channel activation induced by LPS. This interaction may explain the improvement of vascular reactivity to PE, mediated by DEX, in LPS‐treated rats, highlighting a new pharmacological activity to the well‐known anti‐inflammatory properties of glucocorticoids.British Journal of Pharmacology (2003) 140 , 91–96. doi: 10.1038/sj.bjp.0705406