Effects of prolonged high-altitude exposure on peripheral adrenergic receptors in young healthy volunteers

Abstract

The regulation of adrenergic receptors during hypoxia is complex, and the results of published reports have not been consistent. In the present study blood cell adrenoceptor characteristics at sea level (SL) before and after prolonged exposure to high altitude (HA) were measured in seven trained young male lowlanders. Sympathoadrenal activity and clinical haemodynamic parameters were also evaluated before departure (SLB), after 1 week (HA1) and 4 weeks (HA4) at HA and 1 week after return to sea level (SLA). As compared to pre-departure sea level values, urinary norepinephrine excretion increased significantly during altitude exposure [SLB: 10.26 (3.04) μg · 3 h⁻¹; HA1: 23.2 (4.19) μg · 3 h⁻¹; HA4: 20.3 (8.68) μg · 3 h⁻¹] and fell to pre-ascent values 1 week after return to sea level [SLA: 9 (2.91) μg · 3 h⁻¹]. In contrast, mean urinary epinephrine levels did not increase over time at HA. Both systolic and diastolic blood pressures, as well as heart rate, were increased during HA exposure. The circadian blood pressure and heart rate rhythms were preserved during all phases of altitude exposure. Mean maximal binding (B _max) of the α₂-adrenoceptor antagonist [³H]rauwolscine to platelet membranes was significantly reduced (P < 0.001) after exposure to chronic hypoxia [SLB: 172.6 (48.5) fmol · mg⁻¹ protein versus SLA: 136.8 (56.1) fmol · mg⁻¹ protein] without change in the dissociation constant (K _D). Neither the lymphomonocyte β₂-adrenoceptor B _max [SLB: 38.5 (13.6) fmol · mg⁻¹ protein, versus SLA: 32.4 (12.1) fmol · mg⁻¹ protein] nor the K _D for [³H]dihydroalprenolol was affected by chronic hypoxia. Cyclic AMP (adenosine 3′,5′-cyclic monophoshate) generation in lymphomonocytes by maximal isoproterenol stimulation was not modified after prolonged HA exposure. In conclusion, the down-regulation of α₂-adrenoceptors appears to be an important component of the adrenergic system response to HA exposure.