β₂-adrenoceptor modulation in COPD and its potential impact on cardiovascular comorbidities

COPD and chronic CVDs often coexist and pharmacological modulation of β₂-adrenoceptor (β₂-AR) function remains a critical issue in the management of these diseases. Activation of the β₂-AR, a requisite mechanism of action, promotes bronchodilation that improves COPD-related health-outcome measures, such as quality of life, dyspnoea, exercise capacity and, mainly, the number and severity of exacerbations. Nevertheless, recent findings suggest that β₂-AR stimulation induces physiological and pathological signals in the lung. β-AR found in the heart play an important role in the control of the cardiovascular system, but the changes in cardiac autonomic function in CVDs may contribute to an increased cardiac risk associated with inhaled β₂-AR agonist treatment. New insights on the mechanism of action of β₂-AR agonists have engendered rethinking of the efficacy and safety of β₂-AR activation in the management of CVD and COPD. The future development of novel synthetic β₂-AR agonists could avoid adverse reactions by modulating tertiary and quaternary conformations that alter β₂-AR phosphorylation and desensitisation.