Alveolar air and oxidative metabolic demand during exercise in healthy adults: the role of single-nucleotide polymorphisms of the β₂AR gene

The predominating β-adrenergic receptor subtype expressed on human alveolar tissue is the β₂AR. The homozygous arginine (Arg16Arg) single-nucleotide polymorphism (SNP) at codon 16 of the β₂AR gene has been associated with abnormal β₂AR function accompanied by decreased resting alveolar-capillary membrane gas-transfer in certain healthy adults. Although not previously studied in the context of the β₂AR gene, pulmonary gas-transfer is also influenced by alveolar volume (V_A) and with it the availability of alveolar surface area, particularly during exercise. Small V_A implies less alveolar surface area available for O₂ transport. We tested the following hypothesis in healthy adults during exercise: compared with Gly16Gly and Arg16Gly β2AR genotypes, Arg16Arg will demonstrate reduced V_A and ventilation (V̇_A) relative to V̇_E and oxidative metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16), Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40%-peak workload) and moderate (9-min, 75%-peak workload) intensity exercise. We derived V_A and V̇_A using “ideal” alveolar equations via arterialized gases combined with breath-by-breath ventilation and gas-exchange measurements; whereas steady-state V̇O₂ was used in metabolic equations to derive exercise economy (EC = workload÷V̇O₂). Variables at rest did not differ across β₂AR genotype. Strongest β₂AR genotype effects occurred during moderate exercise. Accordingly, while V̇_E did not differ across genotype (P > 0.05), decreased in Arg16Arg versus Arg16Gly and Gly16Gly were V̇O₂ (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m²), respectively, both P < 0.05), V̇_A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and V_A (1.43 ± 0.37, 1.95 ± 0.61, 1.93 ± 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 ± 0.23, 1.99 ± 0.30, and 1.94 ± 0.26 kcal/(L·m²), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β₂AR genotype plays a role in the loss of oxidative metabolic efficiency coupled with an inadaptive V_A and, hence, smaller alveolar surface area available for O₂ transport during submaximal exercise in healthy adults.