Hemorrhage and resuscitation has been recognized as an exclusively destructive process which results in multiple organ dysfunction. Although it is well established that endogenous adaptation (preconditioning) mechanisms exist, it is unknown whether hemorrhage and resuscitation induces endogenous adaptive/protective mechanisms in the heart. Furthermore, alpha 1-adrenoceptors and nuclear factor kappa B (NF kappa B) have each been implicated in stress-induced signal transduction; however, whether they might be involved in hemorrhage-induced adaptive signal transduction remains unknown. This study tests the hypothesis that H/R activates myocardial NF kappa B and results in myocardial adaptation via alpha 1-adrenoceptors. Rats were briefly (10 min) hemorrhaged to 35 mmHg and resuscitated, sham operated, or neither, with and without prior alpha 1-adrenoceptor inhibition (prazosin). Hearts were then isolated and either probed for NF kappa B activation or subjected to a second insult consisting of global normothermic I/R (20 min/40 min). Antecedent hemorrhage and resuscitation activated myocardial NF kappa B and improved left ventricular developed pressure, coronary flow, and end diastolic pressure following ischemia-reperfusion (P < 0.05, ANOVA with Bonferroni-Dunn). Hemorrhage-induced adaptation was abolished by prior alpha 1-adrenoceptor blockade. This study constitutes the initial demonstration that H/R activates myocardial NF kappa B and induces adaptive signal transduction against ischemia-reperfusion injury.