Background—On the basis of the presence of β₂-receptors within the sympathetic nervous system, β₂-stimulation may increase cardiac sympathetic outflow. We addressed the hypothesis that sympathoexcitatory β₂-receptors are present in the human left ventricle.

Methods and Results—The β₂-agonist salbutamol was infused into the left coronary artery in 3 groups of patients: group 1 (n=9, no β-blocker therapy), group 2 (n=7, β₁-selective blockade with atenolol), and group 3 (n=6, nonselective β-blockade with nadolol). Left ventricular +dP/dt in response to increasing concentrations of salbutamol was measured in all groups, and cardiac norepinephrine spillover was measured in group 1. There were no systemic hemodynamic changes in any group. Salbutamol resulted in a 44±6% increase in +dP/dt in group 1, a 25±6% increase in group 2 (P<0.05 versus group 1), and no increase in group 3. Salbutamol also resulted in a 124±37% increase in cardiac norepinephrine spillover in group 1 (P<0.05).

Conclusions—Evidence that salbutamol increased norepinephrine release from cardiac sympathetic nerves was provided by the observations that atenolol suppressed the salbutamol inotropic response, demonstrating that this response was mediated in part by β₁-receptors and that salbutamol also resulted in an increase in cardiac norepinephrine spillover. This result provides in vivo evidence, in humans, for the role of sympathoexcitatory cardiac β₂-receptors.