Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males

 Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signalling, the primary mechanism mediating sympathetic vasoconstriction at sea-level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intra-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-βblockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344m) and following three-weeks at HA (4,380m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34±15%, vs HA; +3±18%; P<0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45±18% vs HA: -28±11%; P=0.009) and high (ΔFVC: SL: -47±20%, vs HA: -35±20%; P=0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC (P=0.500) and combined α-βblockade induced a similar vasodilatory response at SL and HA (P=0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P=0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-βblockade at SL (ΔFVC: Control: -27±128 vs α-βblockade: +19±23%; P=0.0004), but unaffected at HA (ΔFVC: Control: -20±22 vs α-βblockade: -23±11%; P=0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α1-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although, the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.