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 alpha-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male low-landers, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (Delta FVC) during 1) incremental intra-arterial infusion of phenylephrine to assess alpha(1)-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of beta-adrenergic and alpha-adrenergic antagonists propranolol and phentolamine (alpha-beta-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (Delta FVC: SL: -34 +/- 15%, vs. HA; +3 +/- 18%; P < 0.0001) and markedly attenuated the response to medium (Delta FVC: SL: -45 +/- 18% vs. HA: -28 +/- 11%; P = 0.009) and high (Delta FVC: SL: -47 +/- 20%, vs. HA: -35 +/- 20%; P = 0.041) doses. Blockade of beta b-adrenergic receptors alone had no effect on resting FVC (P = 0.500) and combined alpha-beta-blockade 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 alpha-beta-blockade at SL (Delta FVC: Control: -27 +/- 128 vs. alpha-beta-blockade: +19 +/- 23%; P = 0.0004), but unaffected at HA (Delta FVC: Control: -20 +/- 22 vs. alpha-beta-blockade: -23 +/- 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates alpha(1)-adrenergic receptor responsiveness; however, resting alpha-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.