Role of beta 1-receptors and vagal tone in cardiac inotropic and chronotropic responses to a beta 2-agonist in humans.
To assess the contribution of cardiac beta 2-receptors in the cardiac inotropic and chronotropic responses to a beta 2 agonist, terbutaline was infused (0.2 and 0.4 micrograms/kg/min), alone or after pretreatment with either oral atenolol 50 mg or atropine 0.04 mg/kg i.v. or both in six healthy subjects with a multiple crossover design. Terbutaline 0.2 micrograms/kg/min increased heart rate by 15 +/- 2 beats/min, and this response doubled (to 29 +/- 3 beats/min) when the terbutaline infusion followed atropine pretreatment, whereas atenolol pretreatment had no significant effect. Heart rate increased by 44 +/- 2 beats/min in response to terbutaline 0.4 micrograms/kg/min. This response was not affected by atropine. Pretreatment with atenolol diminished the chronotropic response to the higher dose of terbutaline to 27 +/- 4 beats/min. The inotropic response (i.e., changes in pressure: volume ratio) to terbutaline 0.2 micrograms/kg/min was potentiated by atropine (from 1.6 +/- 0.3 to 3.4 +/- 0.8 mm Hg/ml), whereas atenolol pretreatment had no effect. At the higher dose of terbutaline, atropine pretreatment had no additional effect, whereas atenolol decreased the rise in pressure: volume ratio from 6.0 +/- 1.4 to 2.6 +/- 1.0 mm Hg/ml. The results with atenolol pretreatment indicate that cardiac beta 1 responses are associated with the higher dose of terbutaline, either through direct beta 1 stimulation or indirectly from presynaptic beta 2 activity. The atropine data show that vagal tone actually increased during the terbutaline infusions, blunting the cardiac effects. The results of the present study support the existence of functional chronotropic, as well as inotropic, beta 2 receptors in the healthy human heart.
Levine
M A
MA
Division of Clinical Pharmacology, Toronto Western Hospital, Ontario, Canada.
Leenen
F H
FH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001262:Atenolol / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001774:Blood Chemical Analysis; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D001262:Atenolol; D001285:Atropine; D013726:Terbutaline