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Global REACH Expedition: Chronic Hypoxia Attenuates the Contribution α‐Adrenergic Receptors to Sympathetic Transduction in Exercising Humans
Author(s) -
Hearon Christopher M,
Hansen Alex B,
Moralez Gilbert,
Romero Steven A,
Levine Benjamin D,
Lawley Justin S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.562.11
Subject(s) - medicine , vasoconstriction , vasodilation , phentolamine , adrenergic , endocrinology , hypoxia (environmental) , sympathetic nervous system , forearm , adrenergic antagonist , cardiology , blood pressure , receptor , chemistry , anatomy , organic chemistry , oxygen
Acute exposure to hypoxia causes a rise in sympathetic nervous system activity (SNA) that restrains peripheral vasodilation. In normoxia, α‐adrenergic receptors are the primary mechanism eliciting vasoconstriction in response to increased SNA at rest and during exercise. However, exposure to chronic hypoxia (CH) causes a sustained and marked increase in SNA that is offset by reduced neurovascular transduction (vasoconstriction). Data from animal models indicate that CH blunts α‐adrenergic vasoconstrictor signaling, termed ‘hypoxic sympatholysis’. In humans it is unknown how CH alters α‐adrenergic restraint of skeletal muscle vascular tone at rest and during exercise. Purpose To test the hypothesis that CH reduces α‐adrenergic restraint of forearm skeletal muscle vascular tone at rest and during sympathoexcitation in response to cycle exercise. Method In 9 healthy lowland natives, we measured forearm blood flow (Doppler ultrasound), mean arterial pressure (MAP, intra‐arterial catheter), heart rate (HR, ECG) and calculated changes in vascular conductance (ΔFVC) during semi‐recumbent cycle exercise (60% VO 2 max) at baseline (BL: 344m) and after three weeks sojourn at high‐altitude (CH: 4,380m). Sympathetic α‐adrenergic restraint of vascular tone was assessed via intra‐arterial infusion of phentolamine (PHT, α‐adrenergic antagonist) to achieve local forearm α‐adrenoceptor blockade. All data are quantified as mean ± SD. Results At rest, FVC was not lower in CH (BL: 38.0 ± 9.3 vs. CH: 32.6 ± 15.1 ml/100 mmHg/min; p=0.17). Local α‐adrenergic blockade increased FVC at BL and in CH (ΔFVC during PHT: BL: 70.0 ± 35.5 vs. CH: 87.7 ± 69.2 ml/100mmHg/min; P=0.59), indicative of significant residual basal α‐adrenergic restraint of vascular tone in CH. In contrast, the forearm vasoconstrictor response to 60% cycle exercise was attenuated by ~50% in CH (%ΔFVC during exercise: BL: −42.7 ± 29.6 vs. CH: −21.6 ± 19.4; P<0.05). Local α‐adrenergic blockade attenuated the vasoconstrictor response to exercise by 80% at BL (%ΔFVC during exercise: BL: −38.7 ± 34.2 vs. PHT: −6.1 ± 26.3; P<0.05). However, local α‐adrenergic blockade had no impact on the vasoconstrictor response to exercise in CH (%ΔFVC during exercise: CH: −21.6 ± 19.4 vs. PHT: −18.9 ± 12.1; P=0.77). Conclusion Exposure to CH did not significantly alter basal α‐adrenergic restraint of forearm skeletal muscle vascular tone. However, CH attenuates the forearm vasoconstrictor response to cycle exercise, and the contribution of α‐adrenergic receptor‐mediated vasoconstriction is abolished, indicating a reliance on alternative vasoconstrictor mechanisms. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .