It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial PO2 and PCO2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand (MVO2). We hypothesized that the coronary vascular response to PO2 and PCO2 would be attenuated in healthy men when MVO2 was attenuated with β1-adrenergic receptor blockade. Healthy men (n=11; age: 25 {plus minus} 1 years) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized, crossover study, and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and following 5-min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. Rate pressure product (RPP) and left-ventricular mechanical energy (MELV) were calculated as indices of MVO2. All gas manipulations augmented RPP, MELV, and LADV but only RPP and MELV were attenuated (4-18%) following β1-adrenergic receptor blockade (P<0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response when compared to placebo during poikilocapnic hypoxia (29.4{plus minus}2.2 vs. 27.3{plus minus}1.6 cm/s) and isocapnic hypoxia (29.5{plus minus}1.5 vs. 30.3{plus minus}2.2 cm/s). Hypercapnic hypoxia elicited a feed-forward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial PO2 on coronary vascular regulation that is independent of MVO2
