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Journal of Animal Science, Vol 73, Issue 6 1754-1765, Copyright © 1995 by American Society of Animal Science
JOURNAL ARTICLE |
A. J. Hoey, M. L. Matthews, T. W. Badran, G. G. Pegg and M. N. Sillence
Tropical Beef Centre, Rockhampton, Queensland, Australia.
The mechanism through which the repartitioning agent clenbuterol increases heart rate was investigated. First, the relative importance of the beta 1- and beta 2-adrenoceptors was established in rat and bovine right atria in vitro. The positive chronotropic and inotropic effects of (+/-)isoproterenol in rat and bovine right atria, respectively, were markedly antagonized (P < .001) by the beta 1-adrenoceptor antagonist CGP 20712A but were antagonized less by the beta 2-adrenoceptor antagonist ICI 118 551 in rat (P < .01), but not in bovine atria, indicating a major role of the beta 1-adrenoceptors. Clenbuterol was only a partial agonist in rat right atria, increasing heart rate at high concentrations through stimulation of beta 1-adrenoceptors. In studies in vivo, clenbuterol decreased the plasma potassium concentration (P < .05) and increased the plasma glucose concentration (P < .05). Clenbuterol also reduced diastolic blood pressure (P < .01) and increased heart rate (P < .001). The increase in heart rate was not due to direct stimulation of cardiac beta 1-adrenoceptors by clenbuterol but was consistent with a reflex response to beta 2-adrenoceptor-mediated hypotension. This would have caused the activation of baroreceptors, which in turn would have resulted in both the release of norepinephrine to stimulate cardiac beta 1-adrenoceptors and the inhibition of cholinergic input to the heart. Thus, the effects of clenbuterol could be eliminated completely by ICI 118 551 or reduced by approximately 50% using CGP 20712A. The combination of treatment of clenbuterol and CGP 20712A could be useful. It may allow the full repartitioning effects seen with the beta 2-agonist alone, but with a markedly attenuated effect on the heart. Such a treatment regimen may also help reduce the increased energy expenditure and loss of appetite seen following the initial administration of clenbuterol.
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