BETA-ADRENERGIC STIMULATION CAUSES CARDIOCYTE APOPTOSIS - INFLUENCE OF TACHYCARDIA AND HYPERTROPHY

To establish whether catecholamines per se in the absence of significa nt increases in systolic load induce myocardial damage via apoptosis, rats were treated with vehicle or isoproterenol (400 mu g.kg(-1).h(-1) ). Apoptotic cardiocytes (Apo) were identified in paraffin-embedded se ctions using terminal deoxynucleotide transferase-mediated dUTP nick. end labeling. Results were confirmed using an independent ligase assay . Systolic blood pressures were comparable in isoproterenol-treated an d control rats. Twenty-four hours of treatment with isoproterenol resu lted in significant numbers of Apo compared with control [7.9 +/- 2.5 vs. 0.3 +/- 0.3 (SE) cm(-2), P < 0.05]. A cohort of animals was subjec ted to ventricular pacing to induce a tachycardia equivalent to that i nduced by isoproterenol, and these animals did not show an increase in Ape. The left ventricular hypertrophy induced by 2 wk of abdominal ao rtic banding also increased Apo (similar to 7.2-fold); however, 24 h o f isoproterenol infusion did not induce additional Apo in these rats. Thus catecholamines, in the absence of altered systolic load, induce A po which is not mediated solely by tachycardia. Left ventricular hyper trophy secondary to abdominal aortic banding is associated with Ape, b ut this does not increase sensitivity to isoproterenol-induced Ape.