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 β-adrenoceptor (β-AR) stimulation might be different dependent on β₁- or β₂-AR stimulation.

For this purpose we studied, in six male healthy volunteers (aged 28±1 years), the effects of atropine infusion (0.15 μg/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 β₁-and β₂-AR), terbutaline (25–150 ng/kg/min, increasing HR and QS₂c via β₂-AR), adrenaline (20–160 ng/kg/min, increasing HR via β₂- and QS₂c via β₁-AR) and bicycle exercise in supine position (increasing HR and QS₂c via β₁-AR). The three β-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 β-AR agonists and exercise; increases were larger for β₂-AR (terbutaline, adrenaline) mediated effects than for β₁-AR (exercise) mediated effects. Moreover, atropine enhanced β-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, β₁-and β₂-AR mediated stimulation evoked HR-increases are composed of two components: increases via direct β-AR stimulation and simultaneously decreases via increase in vagal tone. In addition, β-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.