During exercise, β-
adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-
adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise
hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial
oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that β1 blockade with
esmolol improves coronary exercise
hyperemia compared with nonselective β-blockade with
propranolol. Eight healthy young men received
intravenous infusions of
esmolol,
propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until
fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t-tests.
Esmolol (Δ = 3296 ± 1204) and
propranolol (Δ = 2997 ± 699) caused similar reductions in peak RPP compared with saline (Δ = 5384 ± 1865). In support of our hypothesis, ΔCBV with
esmolol was significantly greater than with
propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing ΔCBV to ΔRPP. In summary, not only does selective β1 blockade reduce myocardial
oxygen demand during exercise, but it also unveils β2-receptor-mediated coronary exercise
hyperemia.NEW & NOTEWORTHY In this study, we evaluated the role of vascular β1 vs. β2 receptors in coronary exercise
hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with
esmolol compared with
propranolol. These findings increase our understanding of the individual and combined roles of coronary β1 and β2
adrenergic receptors in humans.