Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 461, Issue 2-3, Pages 171-179Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(03)01314-1
Keywords
cardiomyocyte; cyclo-oxygenase-2; cytokine; annexin-1; glucocorticoid; nitric oxide (NO) synthase 2
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We have previously shown that the glucocorticoid dexamethasone prevents the cardiodepressant actions of interferon-gamma plus lipopolysaccharide in cardiac tissue in vitro. We now demonstrate that an N-terminal fragment of annexin-l (Ac2-26, 1 muM), a putative mediator of glucocorticoid actions, completely protects against interferon-gamma + lipopolysaccharide-induced depression of the inotropic response to isoprenaline in rat isolated papillary muscles. However, Ac2-26 does not preserve resting contractile function. Fifteen hours incubation with interferon-gamma + lipopolysaccharide also markedly induced mRNA expression (by real time polymerase chain reaction, PCR) of both the nitric oxide synthase 2 (NOS2) isoform of nitric oxide synthase (by 6.7 +/- 1.7-fold, P<0.01) and cyclo-oxygenase-2 (by 3.4 +/- 0.6-fold, P < 0.05) in cardiomyocytes. Pretreatment with Ac2-26 (I muM) prevented the induction of cyclo-oxygenase-2 mRNA, but not NOS2 mRNA, whereas dexamethasone (1 muM) suppressed the expression of both NOS2 mRNA and cyclo-oxygenase-2 mRNA. Co-incubation of dexamethasone with an anti-annexin-l antibody did not allenuate the suppression of NOS2 mRNA. Thus, Ac2-26 reproduces some, but not all, of the cardioprotective effects of glucocorticoids in vitro in the absence of neutrophils. These protective actions are independent of changes in NOS2 expression. (C) 2003 Elsevier Science B.V. All rights reserved.
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