Esmolol infusion versus propranolol infusion: effects on heart rate and blood pressure in healthy volunteers

Despite its widespread clinical use, the β1 adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research and the effective dose (compared to the nonselective β-blocker propranolol) is unclear. In four separate studies, we used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate (HR)- lowering effect of esmolol compared to propranolol and saline in healthy humans. In Cohort 1, both esmolol (ΔHR: 57 ± 6) and propranolol (ΔHR: 56 ± 7) attenuated exercise tachycardia compared to saline (ΔHR: 88 ± 17). In Cohort 2, we found that ΔHR to exercise was similar 5 minutes (ΔHR: 57 ± 9) and 60 minutes (ΔHR: 55 ± 9) after starting the esmolol maintenance infusion. In Cohort 3 we confirmed that the HR-lowering effect of esmolol disappears 45 minutes after stopping the maintenance infusion. In Cohort 4, changes in femoral blood flow and hematological parameters in response to epinephrine infusion were comparable between esmolol and saline infusion indicating that our esmolol infusion paradigm does not block β2 receptors. Collectively, our data indicate that infusing ~160 mg of esmolol (range 110 to 200 mg in the 5 minutes prior to exercise) acutely and selectively blocks β1 adrenergic receptors in healthy humans. Additionally, β1 receptors remain blocked 60 minutes later if a maintenance infusion of ~0.2 mg/kg total body mass/min continues. The current data lay the foundation for future studies to evaluate β1 versus β2 control of the circulation in humans.