ALPHA-ADRENERGIC ACTIVATION OF MYOCARDIAL NF-KAPPA-B DURING HEMORRHAGE

Hemorrhage and resuscitation has been recognized as an exclusively des tructive process which results in multiple organ dysfunction. Although it is well established that endogenous adaptation (preconditioning) m echanisms exist, it is unknown whether hemorrhage and resuscitation in duces endogenous adaptive/protective mechanisms in the heart. Furtherm ore, alpha(1)-adrenoceptors and nuclear factor kappa B (NF kappa B) ha ve 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 i solated and either probed for NF kappa B activation or subjected to a second insult consisting of global normothermic I/R (20 min/40 min). A ntecedent 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 init ial demonstration that H/R activates myocardial NF kappa B and induces adaptive signal transduction against ischemia-reperfusion injury. (C) 1997 Academic Press.