Global REACH 2018: increased adrenergic restraint of blood flow preserves coupling of oxygen delivery and demand during exercise at high-altitude.

Chronic exposure to hypoxia (high-altitude, HA; >4000 m) attenuates the vasodilatory response to exercise and is associated with a persistent increase in basal sympathetic nerve activity (SNA). The mechanism(s) responsible for the reduced vasodilatation and exercise hyperaemia at HA remains unknown. We hypothesized that heightened adrenergic signalling restrains skeletal muscle blood flow during handgrip exercise in lowlanders acclimatizing to HA. We tested nine adult males (n = 9) at sea-level (SL; 344 m) and following 21–28 days at HA (∼4300 m). Forearm blood flow (FBF; duplex ultrasonography), mean arterial pressure (MAP; brachial artery catheter), forearm vascular conductance (FVC; FBF/MAP), and arterial and venous blood sampling (O2 delivery (DO2 ) and uptake (V...O2 )) were measured at rest and during graded rhythmic handgrip exercise (5%, 15% and 25% of maximum voluntary isometric contraction; MVC) before and after local α- and β-adrenergic blockade (intra-arterial phentolamine and propranolol). HA reduced ΔFBF (25% MVC: SL: 138.3 ± 47.6 vs. HA: 113.4 ± 37.1 ml min−1; P = 0.022) and ΔV...O2 (25% MVC: SL: 20.3 ± 7.5 vs. HA: 14.3 ± 6.2 ml min−1; P = 0.014) during exercise. Local adrenoreceptor blockade at HA restored FBF during exercise (25% MVC: SLα–β blockade: 164.1 ± 71.7 vs. HAα–β blockade: 185.4 ± 66.6 ml min−1; P = 0.947) but resulted in an exaggerated relationship between DO2 and V...O2 (DO2 /V...O2 slope: SL: 1.32; HA: slope: 1.86; P = 0.037). These results indicate that tonic adrenergic signalling restrains exercise hyperaemia in lowlanders acclimatizing to HA. The increase in adrenergic restraint is necessary to match oxygen delivery to demand and prevent over perfusion of contracting muscle at HA. [ABSTRACT FROM AUTHOR]