Alveolar air and oxidative metabolic demand during exercise in healthy adults: the role of single‐nucleotide polymorphisms of the β (2) AR gene

The predominating β‐adrenergic receptor subtype expressed on human alveolar tissue is the β (2) AR. The homozygous arginine (Arg16Arg) single‐nucleotide polymorphism (SNP) at codon 16 of the β (2) AR gene has been associated with abnormal β (2) AR function accompanied by decreased resting alveolar‐capillary membrane gas‐transfer in certain healthy adults. Although not previously studied in the context of the β (2) AR 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 O(2) 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 V̇O(2) was used in metabolic equations to derive exercise economy (EC = workload÷V̇O(2)). Variables at rest did not differ across β (2) AR genotype. Strongest β (2) AR 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 V̇O(2) (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m(2)), 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·m(2)), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β (2) AR 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 O(2) transport during submaximal exercise in healthy adults.