Esmolol Infusion Versus Propranolol Infusion: Effects On Heart Rate And Blood Pressure In Healthy Volunteers

Despite its widespread clinical use, the +/- beta 1-adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research, and the effective dose of esmolol (compared with the nonselective(beta-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 with propranolol and saline in healthy humans. In cohort 1, both esmolol ((Delta HR 57((+/- 6 beats/min) and propranolol (Delta HR 56 +/- 7 beats/min) attenuated exercise tachycardia compared with saline (Delta HR 88 +/- 17 beats/min). In cohort 2, we found that the HR response to exercise was similar at 5 min (Delta HR 57 +/- 9 beats/min) and 60 min (Delta HR 55 +/- 9 beats/min) after initiation of the esmolol maintenance infusion. In cohort 3, we confirmed that the HR-lowering effect of esmolol disappeared 45 min after termination of the maintenance infusion. In cohort 4, changes in femoral blood flow and hematological parameters in response to epinephrine infusion were not different between esmolol and saline infusion, indicating that our esmolol infusion paradigm does not block beta 2-receptors. Collectively, our data indicate that infusion of similar to 160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks beta 1-receptors in healthy humans. Additionally, beta 1-receptors remain blocked 60 min later if a maintenance infusion of similar to 0.2 mg u kg total body mass -1 u min -1 continues. The current data lay the foundation for future studies to valuate beta 1-vs. -2-receptor control of the circulation in humans. NEW & NOTEWORTHY We used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart ratelowering effect of esmolol compared with propranolol and saline in healthy humans. Collectively, our data indicate that infusion of 160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks 1-adrenergic receptors. These infusion parameters can be used in future experiments to evaluate 1-vs. 2-receptor control of the circulation in humans.