Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

Abstract

Background: Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β(2)AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β(2)AR density on lymphocytes and indices of lung water in healthy humans exposed to ≈ 17 h of hypoxia (FIO2 = 12.5% in a hypoxia tent).

Methods: Thirteen adults (mean ± SEM; age=31 ± 3 years, BMI=24 ± 1 kg/m(2), VO2 Peak = 40 ± 2 ml/kg/min ) participated. Pulmonary function, CT derived lung tissue volume (V(tis)-tissue, blood and water), lung diffusing capacity for carbon monoxide (D(CO)) and nitric oxide (D(NO)), alveolar-capillary conductance (D(M)), pulmonary capillary blood volume (V(c)) and lung water (CT V(tis)-V(c)) were assessed before and after ≈ 17 h normobaric hypoxia (FIO2 = 12.5%). β(2)AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed.

Results: After 17 h hypoxia, SaO2 decreased from 97 ± 1 (normoxia) to 82 ± 4% and RVSP increased from 14 ± 3 (normoxia) to 29 ± 2 mmHg (p<0.05) with little change in Q or BP. V(c) and D(M) both increased with hypoxia with a small increase in D(M)/V(c) ratio (p>0.05). CT V(tis) decreased and lung water was estimated to decline 7 ± 13%, respectively. β(2)AR density averaged 1497 ± 187 receptors/lymphocyte and increased 21 ± 34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β(2)AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water.

Conclusions: Lung water decreases with 17 h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.