beta-adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy.
To establish whether catecholamines per se in the absence of significant increases in systolic load induce myocardial damage via apoptosis, rats were treated with vehicle or isoproterenol (400 microg . kg-1 . h-1). Apoptotic cardiocytes (Apo) were identified in paraffin-embedded sections 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 and control rats. Twenty-four hours of treatment with isoproterenol resulted 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 subjected to ventricular pacing to induce a tachycardia equivalent to that induced by isoproterenol, and these animals did not show an increase in Apo. The left ventricular hypertrophy induced by 2 wk of abdominal aortic banding also increased Apo ( approximately 7. 2-fold); however, 24 h of isoproterenol infusion did not induce additional Apo in these rats. Thus catecholamines, in the absence of altered systolic load, induce Apo which is not mediated solely by tachycardia. Left ventricular hypertrophy secondary to abdominal aortic banding is associated with Apo, but this does not increase sensitivity to isoproterenol-induced Apo.
Shizukuda
Y
Y
Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Buttrick
P M
PM
Geenen
D L
DL
Borczuk
A C
AC
Kitsis
R N
RN
Sonnenblick
E H
EH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal; D017209:Apoptosis; D002304:Cardiac Pacing, Artificial; D003250:Constriction; D011088:DNA Ligases / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D003856:Deoxyuracil Nucleotides; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013610:Tachycardia / Q000473:pathology*
D000318:Adrenergic beta-Agonists; D003856:Deoxyuracil Nucleotides; D011943:Receptors, Adrenergic, beta; C027078:deoxyuridine triphosphate; D004253:DNA Nucleotidylexotransferase; D011088:DNA Ligases; D007545:Isoproterenol