Abstract
The contribution of Adenosine (ADO) to exercise hyperemia remains controversial and it is unknown whether ADO can evoke the prolonged vasodilation seen during exercise bouts. Therefore, we tested hypotheses in the human forearm during 3 h of intra‐arterial high dose ADO infusion: (1) skeletal muscle blood flow would wane over time; (2) exercise hyperemic responses during ADO administration would be unaffected compared to baseline. Using sodium nitroprusside (SNP), we tested parallel hypotheses regarding nitric oxide (NO) in a separate group of participants. Seventeen young healthy participants (ADO: n = 9; SNP: n = 8) performed multiple rhythmic handgrip exercise bouts (20% of maximum), two during saline and five during 3 h of continuous drug infusion. Five minutes of ADO infusion resulted in a ~5‐fold increase in forearm vascular conductance (FVC; 4.8 ± 0.6 vs. 24.2 ± 3.2 mL/min/100 mmHg, P < 0.05). SNP caused a ~4‐fold increase (4.4 ± 0.6 vs. 16.6 ± 2 mL/min/100 mmHg, P < 0.05). FVC did not wane over time with ADO (24.2 ± 3.2 and 22 ± 1.2 mL/min/100 mmHg [P > 0.05]) or SNP (16.6 ± 2 and 14.1 ± 2.4 mL/min/100 mmHg [P > 0.05]) at 5 versus 150 min. Superimposed exercise during ADO or SNP infusions evoked marked and consistent additional dilation over the course of the infusions. Our findings demonstrate that in humans there is no reduction in endothelial or vascular smooth muscle responsiveness to the exogenous vasodilatory metabolites ADO and NO. Additionally, even in the presence of an exogenous vasodilator, superimposed exercise can cause significant hyperemia.
Highlights
Skeletal muscle blood flow increases during exercise in order to match the metabolic demands of the exercising muscle (Shepherd 1983; Saltin et al 1998; Joyner and Casey 2015)
We showed that prolonged infusions of adenosine triphosphate (ATP), a vasoactive metabolite that may play a significant role in exercise hyperemia, can evoke marked and prolonged vasodilation in the human forearm (Shepherd et al 2016)
In recent years the role of ADO during exercise hyperemia has been debated due to the following observations: (1) blocking ADO deaminase does not increase the blood flow to exercising muscles (Martin et al 2007), (2) there is a dichotomous response in humans to exogenous ADO infusion, with “responders” and “non-responders” despite similar exercise hyperemia between the groups (Martin et al 2006a), (3) even though ADO-mediated vasodilation is significantly blunted with nitric oxide synthase (NOS) inhibitors in responders; the exercise hyperemia is not blunted during NOS inhibition in either responders or non-responders (Martin et al 2006a), and (4) data from our laboratory have shown that the response to exogenous ADO administration does not correlate to the hyperemic responses to exercise (Martin et al 2007)
Summary
Skeletal muscle blood flow increases during exercise in order to match the metabolic demands of the exercising muscle (Shepherd 1983; Saltin et al 1998; Joyner and Casey 2015). In recent years the role of ADO during exercise hyperemia has been debated due to the following observations: (1) blocking ADO deaminase does not increase the blood flow to exercising muscles (Martin et al 2007), (2) there is a dichotomous response in humans to exogenous ADO infusion, with “responders” and “non-responders” despite similar exercise hyperemia between the groups (Martin et al 2006a), (3) even though ADO-mediated vasodilation is significantly blunted with nitric oxide synthase (NOS) inhibitors in responders; the exercise hyperemia is not blunted during NOS inhibition in either responders or non-responders (Martin et al 2006a), and (4) data from our laboratory have shown that the response to exogenous ADO administration does not correlate to the hyperemic responses to exercise (Martin et al 2007) These studies evaluated the role of ADO during shorter periods of vasodilation and exercise. Heart rate (HR) was recorded via a continuous 3-lead electrocardiogram
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