ADRENERGIC STATUS OF HUMANS DURING PROLONGED EXPOSURE TO THE ALTITUDE OF 6,542 M

Adrenergic status of humans during prolonged exposure to the altitude of 6,542 m. J. Appl. Physiol. 76(3): 1055-1059, 1994. - Plasma norepinephrine (NE) concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IF) are blunted. Downregulation of cardiac beta-adrenergic receptors (beta-AR) has been evoked to explain this phenomenon. Chronotropic response was studied at extreme altitude in 10 subjects (4 women, 6 men; aged 35 +/- 6 yr). Observations were made in normoxia (N) and after 1 (H1) and 3 (1-13) wk at 6,542 m. Acclimatization was accomplished by gradual climbing from 4,000 to 6,542 m over 10 days. Plasma NE was obtained at rest and during submaximal exercise. Successive doses of IP (0.02, 0.04, and 0.06 mu g.kg(-1) min(-1)) were infused for 5 min each. Density and affinity of lymphocyte beta(2)-AR were also measured. Increase in HR for maximal dose of IP decreased from 57 +/- 12 to 34 +/- 7 and 37 +/- 10 min(-1) in H1 and H3, respectively (P <0.001 for both). IP dose for which HR rises by 25 min(-1) (I-25) increased from 27 +/- 5 in N to 42 +/- 10 and 43 +/- 17 ng.kg(-1) min(-1) in H1 and H3, respectively (P < 0.001 for both). Arterial O-2 saturation at rest was 98 +/- 2% in N, 72 +/- 6% in H1 (P < 0.001), and 79 +/- 5% in H3 (P < 0.001). The chronotropic response was neither restored nor further attenuated after 3 wk at 6,542 m. Plasma NE levels at rest and during exercise were higher at 6,542 m than values obtained in previous studies at 4,350 and 4,800 m. For a given plasma concentration of NE, HR during exercise decreased with increasing altitude. We observed a positive correlation between plasma NE and I-25 but none between I-25 and arterial O-2 content. Lymphocyte beta(2)-AR density decreased by 45%, with no change in affinity. In conclusion, the observed decrease in chronotropic response seems related to the level of altitude-induced adrenergic activation and not to the severity of hypoxia.