High altitude acclimatization abolished the vasoconstrictor response to low-dose phenylephrine compared to sea level, indicating severely attenuated postjunctional α1-adrenergic receptor responsiveness.
Observational (n=10)
No
Does chronic high-altitude exposure alter α1-adrenergic receptor responsiveness and adrenergic vascular restraint in healthy males?
Altitude acclimatization attenuates α1-adrenergic receptor responsiveness in healthy males, but resting α-adrenergic restraint remains intact due to concurrent resting sympathoexcitation.
Absolute Event Rate: 3% vs -34%
p-value: p=<0.0001
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, 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 α 1 -adrenergic receptor responsiveness and 2) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-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 (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-β-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 α-β-blockade at SL (ΔFVC: Control: −27 ± 128 vs. α-β-blockade: +19 ± 23%; P = 0.0004), but unaffected at HA (ΔFVC: Control: −20 ± 22 vs. α-β-blockade: −23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α 1 -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.
Simpson et al. (Tue,) conducted a observational in Healthy (n=10). High altitude exposure vs. Sea level (344 m) was evaluated on Change in forearm vascular conductance (ΔFVC) to low-dose phenylephrine (p=<0.0001). High altitude acclimatization abolished the vasoconstrictor response to low-dose phenylephrine compared to sea level, indicating severely attenuated postjunctional α1-adrenergic receptor responsiveness.
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