Alpha adrenergic blockade does not change coronary circulation during handgrip exercise or isolated metaboreflex activation in humans

Abstract

Coronary circulation control entails several redundant mechanisms, and is primarily regulated by the myocardial metabolism. Therefore, exercise increases coronary blood flow. Animal studies consistently demonstrate an α‐adrenergic vasoconstriction response in coronary arteries during exercise and metaboreflex activation. Additionally, α‐adrenergic receptor (α‐AR) blockade disrupts the increase of coronary circulation coupled with the metabolic demand. However, whether this α‐adrenergic vasoconstrictory mechanism is present in coronary circulation control during exercise has never been tested in humans. Twenty healthy participants were tested [26±15 yr; 24±1 kg·m−2;1.8±0.1 m2; men (n=11); women (n=9); mean±SE]; Heart rate (HR) was continuously monitored, cardiac output (CO) were estimated from finger photoplethysmography arterial pressure waveform using the modelflow method, and cardiac index (CI) calculated by the ratio between CO and body surface area. Mean arterial pressure (MAP) was calculated by the integration of arterial blood pressure waveform over a cardiac cycle. Myocardial oxygen consumption (MVO2) was estimated applying the following formula: MVO2 = 7.2×10−4 (SBP×HR)+1.43; where SBP is systolic blood pressure. Coronary blood flow peak velocity (CBFVpeak) was measured on the left anterior coronary artery from the parasternal short‐axis view with duplex ultrasound. The protocol consisted in three minutes of rest, three minutes of handgrip exercise, followed by three minutes of post‐exercise occlusion (PEO) and three minutes of recovery; in a control (C) condition and after α1‐AR blockade with prazosin. HR increased during exercise and returned to resting values during the PEO in the control and after the α1‐AR blockade. But α‐AR blockade kept HR higher throughout the protocol. In control condition, MAP increased during exercise (Δ36±2 mmHg) and was elevated after PEO (Δ28±3 mmHg). The α1‐AR blockade blunted the pressure response to grip exercise (Δ27±3 mmHg) and to PEO (Δ16±4 mmHg). CI did not change during grip exercise or PEO, during the control condition or after the α1‐AR blockade. CBFVpeak increased during exercise (CΔ6±1 cm·s−1; Blockade Δ8±1 cm·s−1) and return to resting values with PEO (Δ1±0.8 cm·s−1; Δ0.8±1 cm·s−1), and the α1‐AR blockade did not change this condition. MVO2 increased during exercise (CΔ5.0±0.5; Blockade Δ 6.3±0.6) and return to resting values after PEO (C Δ2.1±0.3; Blockade Δ2.1±0.3), and the α1‐AR blockade did not change this condition. Linear regression shows a significant increase in coronary blood flow velocity with the increase of MVO2 from rest to exercise, in the control session (slope=1.18; R2=0.28; p<0.01) and no effect of α1‐AR receptor blockade was observed (slope=1.10; R2=0.28; p<0.01). Which shows that the α1‐AR receptor blockade did not disrupt the coupling between the coronary circulation and the metabolic demand in humans. Therefore, the neural control of coronary circulation via α1‐AR vasoconstriction seems to play a secondary role in humans, differently as observed in dogs and pigs.Support or Funding InformationCAPES; FAPERJ; CNPq; FINEP