Cardiac Function in Mice Overexpressing the β-Adrenergic Receptor Kinase or a βARK Inhibitor

TLDR

Transgenic mice were generated with cardiac‑specific overexpression of beta‑adrenergic receptor kinase‑1 (beta ARK1) or a beta ARK inhibitor. Beta ARK1 overexpression blunted isoproterenol‑induced left ventricular contractility, reduced adenylyl cyclase activity, and impaired beta‑adrenergic receptor coupling, whereas beta ARK inhibition enhanced contractility, underscoring beta ARK’s pivotal role in myocardial function and its potential relevance to heart failure.

Abstract

Transgenic mice were created with cardiac-specific overexpression of the beta-adrenergic receptor kinase-1 (beta ARK1) or a beta ARK inhibitor. Animals overexpressing beta ARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of beta-adrenergic receptors. Conversely, mice expressing the beta ARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of beta ARK in modulating in vivo myocardial function. Because increased amounts of beta ARK1 and diminished cardiac beta-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of beta ARK in heart disease.