Sex differences in the coronary vascular response to combined chemoreflex and metaboreflex stimulation in healthy humans

New Findings What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signalling and adrenergic activity: does the integration of these signals during acute hypoxia and adrenergic activation differ between sexes? What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. Abstract Coronary hyperaemia is mediated through multiple signalling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants ( n = 32; 16F) underwent three randomized trials of isometric handgrip exercise followed by post‐exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End‐tidal was controlled at (1) normoxic levels throughout the trial, (2) 50 mmHg for the duration of the trial (hypoxia trial), or (3) 50 mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LAD Vmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LAD Vmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LAD Vmean to a greater extent in males compared with females ( P < 0.05), despite a similar increase in cardiac workload. The change in LAD Vmean induced by PECO was similar between sexes in normoxia ( P = 0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs. female: 8.1 (6.3) cm/s; P = 0.02) and reduced in males but not females in acute hypoxia (male: −4.8 (4.5) cm/s vs. female: 0.8 (6.2) cm/s; P = 0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females.