β2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle
In: Journal of applied physiology (1985), Jg. 98 (2005), Heft 4, S. 1379-1386
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Zugriff:
High doses of the β2-adrenergic receptor (AR) agonist clenbuterol can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known whether this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of clenbuterol. Immunohistochemistry was used to detect myocyte-specific apoptosis (detected on cryosections via a caspase 3 antibody and confirmed with annexin V, single-strand DNA labeling, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). Myocyte apoptosis was first detected at 2 h and peaked 4 h after clenbuterol administration. The lowest dose of clenbuterol to induce cardiomyocyte apoptosis was 1 μg/kg, with peak apoptosis (0.35 ± 0.05%; P < 0.05) occurring in response to 5 mg/kg. In the soleus, peak apoptosis (5.8 ± 2%; P < 0.05) was induced by the lower dose of 10 μg/kg. Cardiomyocyte apoptosis was detected throughout the ventricles, atria, and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way, from the apex toward the base. β-AR antagonism (involving propranolol, bisoprolol, or ICI 118551) or reserpine was used to show that clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte β1-AR, whereas in the soleus direct stimulation of the myocyte β2-AR was involved. These data show that, when administered in vivo, β2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through β1- and β2-AR, respectively.
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β2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle
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Autor/in / Beteiligte Person: | BURNISTON, Jatin G ; TAN, Lip-Bun ; GOLDSPINK, David F |
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Zeitschrift: | Journal of applied physiology (1985), Jg. 98 (2005), Heft 4, S. 1379-1386 |
Veröffentlichung: | Bethesda, MD: American Physiological Society, 2005 |
Medientyp: | academicJournal |
Umfang: | print, 50 ref |
ISSN: | 8750-7587 (print) |
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