Cardioprotective actions of an N-terminal fragment of annexin-1 in rat myocardium in vitro.

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-1 (Ac2-26, 1 microM), 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 (1 microM) prevented the induction of cyclo-oxygenase-2 mRNA, but not NOS2 mRNA, whereas dexamethasone (1 microM) suppressed the expression of both NOS2 mRNA and cyclo-oxygenase-2 mRNA. Co-incubation of dexamethasone with an anti-annexin-1 antibody did not attenuate 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.