Cardiovascular effects of clenbuterol are beta 2-adrenoceptor-mediated in steers.
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.
Hoey
A J
AJ
Tropical Beef Centre, Rockhampton, Queensland, Australia.
Matthews
M L
ML
Badran
T W
TW
Pegg
G G
GG
Sillence
M N
MN
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D002417:Cattle / Q000502:physiology*; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000737:chemistry / Q000648:ultrastructure; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000502:physiology*
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; C049763:CGP 20712A; D007545:Isoproterenol; D011188:Potassium; D009638:Norepinephrine; D002976:Clenbuterol