Adrenergic system in high altitude residents

Area of Science:

• Cardiovascular Physiology
• Altitude Physiology
• Adrenergic Pharmacology

Background:

• Heart rate response to isoproterenol is reduced in sea-level natives at high altitude.
• This suggests a downregulation of beta-adrenoceptors due to increased norepinephrine in hypoxic conditions.
• Previous studies indicated a blunted response in sea-level natives during chronic hypoxia.

Purpose of the Study:

• To investigate the heart rate response to isoproterenol infusion in high-altitude natives (HAN) and polycythemic high-altitude subjects (HAP).
• To compare beta-adrenoceptor density in these groups with sea-level natives (SLN) under normoxia and chronic hypoxia (SLH).
• To determine if polycythemia affects adrenergic responsiveness at high altitude.

Main Methods:

• Isoproterenol infusion to determine the dose required to increase heart rate by 25 beats/min (I 25).
• Measurement of beta-adrenoceptor density on lymphocytes.
• Comparison of data from high-altitude populations (3600m) with sea-level natives in normoxia and chronic hypoxia (4800m).

Main Results:

• The isoproterenol dose (I 25) was not significantly different between HAN, HAP, and SLN groups.
• Beta-adrenoceptor density was significantly lower in HAN (39% reduction) and HAP (25% reduction) compared to SLN.
• No adrenergic desensitization was observed in high-altitude natives.

Conclusions:

• High-altitude natives maintain a normal heart rate response to isoproterenol, unlike sea-level natives acclimatizing to hypoxia.
• Reduced beta-adrenoceptor density in high-altitude populations may represent an adaptive mechanism to chronic hypoxia.
• Polycythemia does not appear to influence this adrenergic responsiveness.