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

Cardiovascular diseases or type 2 diabetes mellitus and chronic airway diseases: mutual pharmacological interferences

“… 38 However, β 2 -agonists differentiate into full agonists, such as isoproterenol or formoterol, which completely move the equilibrium in the activated conformation of the β 2 -ARs, partial agonists, such as salmeterol or ultra-LABAs (mainly vilanterol), that bind to and activate β 2 -ARs but are unable to generate the maximum possible response produced by full agonists, and inverse agonists, which are β-AR blockers, such as nadolol, that bind to the same β 2 -ARs binding site as an agonist but induce a pharmacologic response opposite to that agonist, shifting the equilibrium away from the activated conformation of the β 2 -ARs toward an inactive state. 23 , 24 Full and partial agonists can elicit similar downstream effects. Full agonists have a therapeutic benefit over partial agonists during an exacerbation because fewer spare receptors may exist.…”

“…In any case, the heart is a non-target tissue with a lower β 2 -AR density than target tissues, such as airway smooth muscle (ASM). 24 MAChRs reside in both the atria and ventricles but have a greater density in the former, with M 2 -mAChRs being the predominant mAChR subtype in the heart. 25 The levels of M 2 -mAChRs are comparable between the human atrium and ventricle, while the density of M 3 -mAChRs appears ∼10-fold higher in the ventricle than in atrium.…”

“…Tachycardia and arrhythmia can result from reduced parasympathetic nervous system activity. 24 Heart rate mediated by β 2 -AR stimulation increases in the presence of inhibition of cardiac vagal tone caused by a mAChR antagonist due to the decrease or even the absence of the influence of vagal tone on the adrenergic response in the heart. 25 …”

“… 39 In contrast, the heart has a lower β 2 -ARs density than ASM, which may explain why partial agonists have a better safety profile. 24 …”

Guest Editors

“…In this ERS Monograph, we have tried to offer the reader a complete overview of the interaction between pulmonary diseases and CVDs, not only from an epidemiological point of view [1], but also from a pathophysiological [2], and more particularly, clinical and therapeutic point of view. Accordingly, after reviewing some basic concepts, the book has been divided into: firstly, each important group of respiratory diseases and their cardiopulmonary implications [3][4][5][6][7][8][9][10][11][12][13][14]; then to the groups of drugs most used in pulmonology and their potential cardiovascular effects [15][16][17][18][19]; and finally, to future diagnostic challenges in this field [20]. Three clinical cases have also been chosen to illustrate different situations taken from real life, in order to delve more fully into the concepts discussed in this book [21][22][23].…”