In this study, transgenic mice were created with a cardiac-specific overexpression of the β-adrenergic receptor kinase-1 (βARK1) or a βARK inhibitor. Animals overexpressing βARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, a reduction of myocardial adenylyl cyclase activity and reduced functional coupling of the β-adrenergic receptors. On the other hand, mice expressing the βARK inhibitor demonstrated enhanced cardiac contractility in vivo with or without isoproterenol. Patients with heart failure have increased amounts of βARK1 and diminished cardiac β-adrenergic responsiveness; this study in transgenic mice demonstrates the important role of βARK1 in modulating in vivo myocardial function. Thus, these transgenic mice may provide an experimental model to further study the role of βARK and its relation to heart disease and heart failure.
↵1 Koch WJ, Rockman HA, Samama P, Hamilton RA, Bond RA, Milano CA, Lefkowitz RJ. Cardiac function in mice overexpressing the β-adrenergic receptor kinase or a βARK inhibitor. Science. 1995;268:1350-1353.
- Copyright © 1995 by American Heart Association