This review highlights that while multiple receptor systems modulate cardiac function, the beta-adrenergic pathway remains the dominant mechanism for increasing contractility and heart rate in the non-failing human heart.
Catecholamines acting through beta 1- and beta 2-adrenoceptors cause positive inotropic and chronotropic effects in the human heart. In recent years, however, evidence has accumulated that in the human heart also other receptor systems can affect heart rate and/or contractility. Positive inotropic effects can be mediated by receptor systems acting through accumulation of intracellular cAMP (Gs-protein coupled receptors such as 5-HT4-like, histamine H2, and vasoactive intestinal peptide) or by receptor systems acting independent of cAMP possibly through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphosphate pathway (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the non-failing human heart, however, activation of all these receptor systems induces only submaximal positive inotropic effects when compared with those caused by beta-adrenoceptor stimulation, indicating that in humans the cardiac beta-adrenoceptor-Gs-protein-adenylate cyclase pathway is the most powerful mechanism to increase heart rate and contractility. On the other hand, at least three receptor systems acting through inhibition of cAMP formation (Gi-protein coupled receptors) exist in the human heart: muscarinic M2-, adenosine A1-, and somatostatin-receptors. Activation of M2- and A1-receptors causes negative inotropic effects in the non-failing human heart: in atria activation of both receptors causes decreases in basal as well as in isoprenaline-stimulated force of contraction, but in ventricles only isoprenaline-stimulated force of contraction is depressed.
Brodde et al. (Wed,) studied this question.