Role of Dopamine in the Heart in Health and Disease

Abstract

Dopamine has effects on the mammalian heart. These effects can include an increase in the force of contraction, and an elevation of the beating rate and the constriction of coronary arteries. Depending on the species studied, positive inotropic effects were strong, very modest, or absent, or even negative inotropic effects occurred. We can discern five dopamine receptors. In addition, the signal transduction by dopamine receptors and the regulation of the expression of cardiac dopamine receptors will be of interest to us, because this might be a tempting area of drug development. Dopamine acts in a species-dependent fashion on these cardiac dopamine receptors, but also on cardiac adrenergic receptors. We will discuss the utility of drugs that are currently available as tools to understand cardiac dopamine receptors. The molecule dopamine itself is present in the mammalian heart. Therefore, cardiac dopamine might act as an autocrine or paracrine compound in the mammalian heart. Dopamine itself might cause cardiac diseases. Moreover, the cardiac function of dopamine and the expression of dopamine receptors in the heart can be altered in diseases such as sepsis. Various drugs for cardiac and non-cardiac diseases are currently in the clinic that are, at least in part, agonists or antagonists at dopamine receptors. We define the research needs in order to understand dopamine receptors in the heart better. All in all, an update on the role of dopamine receptors in the human heart appears to be clinically relevant, and is thus presented here.

Noise Stress induces Cardiovascular Metabolic Shifts

“…This includes connections to fibrinogen, small G-proteins, and even histones, suggesting a direct influence on cardiac gene transcription without receptor involvement (50). The receptor-independent actions of 5-HT and its positive inotropic effects observed in various mammalian species emphasize its multifaceted role in cardiac physiology and its potential influence on signal transduction and gene expression (51).…”

Multitargeting in cardioprotection: An example of biaromatic compounds

“…or propylbutyldopamine (a D 2 -receptor agonist), suggesting that the D 1 -receptors and the D 2 -receptors in the human heart can directly or indirectly increase the force of heart contraction. [161] 4.10 | Histamine receptors Preclinical and clinical studies using histamine receptor antagonists report improvement in cardiac function. For example, the administration of the H 2 -receptor antagonist famotidine reduced the incidence of HF in humans.…”

“…There are data in patients that noted after intravenous infusion a direct positive inotropic effect of fenoldopam (a D 1 ‐receptor agonist) or propylbutyldopamine (a D 2 ‐receptor agonist), suggesting that the D 1 ‐receptors and the D 2 ‐receptors in the human heart can directly or indirectly increase the force of heart contraction. [ 161 ]…”

Initial characterization of a transgenic mouse with overexpression of the human D1-dopamine receptor in the heart

“…This understanding is complicated by species differences, regional differences and cellular differences in dopamine receptor function in the heart (review: Neumann et al 2023). In the wild type mouse heart, a direct dopamine receptor mediated inotropic or chronotropic effect is currently thought to be missing (Yamaguchi et al 2010).…”

“…The D 5 -receptor was initially named D 1A -receptor indicating a very close similarity of these two receptors. Currently, it remains functionally impossible to discern D 1 -dopamine receptors and D 5 -dopamine receptors with receptor agonists or antagonists because they are so similar in their ligand a nities (Neumann et al 2023): for instance, the D 1 -dopamine receptor agonist SKF 38393 and the D 1dopamine receptor antagonist SCH23390 exhibit practically identical a nities for D 1− dopamine and D 5dopamine receptors in ligand binding studies (Neumann et al 2023). Hence, with pharmacological tools, it is currently impossible to decide whether a functional response in the heart to dopamine is D 1dopamine receptor-or D 5 -dopamine receptor-mediated.…”