Effects of atropine on human cardiac β1- and/ or β2-adrenoceptor stimulation

Abstract

The aim of this study was to find out whether, in humans, the increase in vagal tone accompanying cardiac beta-adrenoceptor (beta-AR) stimulation might be different dependent on beta1- or beta2-AR stimulation. For this purpose we studied, in six male healthy volunteers (aged 28+/-1 years), the effects of atropine infusion (0.15 microg/kg/min continuously) on increase in heart rate (HR) and contractility (determined as shortening of HR-corrected duration of electromechanical systole-QS2c) evoked by infusion of isoprenaline (3.5-35 ng/kg/min, increasing HR and QS2c via beta1-and beta2-AR), terbutaline (25-150 ng/kg/min, increasing HR and QS2c via beta2-AR), adrenaline (20-160 ng/kg/min, increasing HR via beta2-and QS2c via beta1-AR) and bicycle exercise in supine position (increasing HR and QS2c via beta1-AR). The three beta-AR agonists and exercise increased HR and shortened QS2c in a dose- or work-load-dependent manner, respectively. Atropine enhanced HR-increasing effects of all three beta-AR agonists and exercise; increases were larger for beta2-AR (terbutaline, adrenaline) mediated effects than for beta1-AR (exercise) mediated effects. Moreover, atropine enhanced beta-AR agonists-induced QS2c shortening; however, atropine effects on QS2c were markedly less pronounced than on HR. From the results we conclude that, in humans, beta1-and beta2-AR mediated stimulation evoked HR-increases are composed of two components: increases via direct beta-AR stimulation and simultaneously decreases via increase in vagal tone. In addition, beta-AR mediated increases in contractility are also dampened by simultaneous activation of vagal tone but to a lesser extent possibly because human ventricular myocardium is only sparsely parasympathetically innervated.

Loss of M2muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac β-adrenergic sensitivity in larval zebrafish (Danio rerio)

“…18). Indeed, when cardiac muscarinic tone is acutely blocked with atropine, ␤-adrenergic-mediated increases in heart rate are greater (3,17,31), suggesting a blunting effect of vagal tone on the adrenergic response in the heart. There is little information about the effects of chronic lack of vagal tone on cardiac ␤-adrenergic receptor function.…”

The Impact of β 2 Adrenergic Receptor Polymorphisms on the Outcomes in Cardiovascular Diseases

“…52 The Ile164 variant of the β 2 AR gene in endothelial cells loses the ability to mediate cell specific responses to catecholamine. 53,54 To gain better insight on the role of Ile164 on atherosclerosis, Piscione et al showed that adenoviral (Ad) β 2 AR-Ile164 infection reduces isoproterenol mediated Vascular smooth muscle cells (VSMC) proliferation. 55 In humans, vascular responses and heart contractility are altered in subjects carrying the Ile164 variant of the β 2 AR gene compared with wild-type volunteers.…”