β2- but not β1-adrenoceptor activation modulates intracellular oxygen availability

beta-Adrenoceptors (beta-ARs) play a critical role in the regulation of cardiovascular function. Intracellular oxygen homeostasis is crucial for the survival of cardiomyocytes. However, it is still unclear whether beta-AR activation can modulate intracellular oxygen. Here we used mitochondrial and cytosolic target Renilla luciferase to detect intracellular oxygen concentration. Pharmacological experiments revealed that beta(2)-AR activation specifically regulates intracellular oxygen in cardiomyocytes and COS7 cells. This effect was abrogated by inhibitory G protein (G(i)) inhibition, endothelial nitric oxide synthase (eNOS) blockade, and NO scavenging, implicating that the beta(2)-AR-G(i)-eNOS pathway is involved in this regulation. beta(2)-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of beta(2)-AR signalling, thus providing an additional layer of complexity to enforce the specificity of beta(1)-AR and beta(2)-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of beta(2)-AR function, and may have crucial implications for beta(2)-AR signalling regulation.