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 (VA) and with it the availability of alveolar surface area, particularly during exercise. Small VA 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 VA and ventilation (V̇A) relative to V̇E 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 VA and V̇A 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 V̇E 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), V̇A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and VA (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 VA and, hence, smaller alveolar surface area available for O2 transport during submaximal exercise in healthy adults.