(Hypertension. 1999;33:396-401.)
© 1999 American Heart Association, Inc.
Scientific Contribution |
ß-Adrenergic Receptor Kinase-1 Levels in Catecholamine-Induced Myocardial Hypertrophy
Regulation by ß- but not 
1-Adrenergic Stimulation
Correspondence to Walter J. Koch, PhD, Department of Surgery, Duke University Medical Center, Room 472, MSRB, Research Drive, Durham, NC 27710. E-mail koch0002{at}mc.duke.edu
Abstract—Pressure overload
ventricular hypertrophy is accompanied by
dysfunctional ß-adrenergic receptor signaling due to increased levels
of the ß-adrenergic receptor kinase-1, which
phosphorylates and desensitizes ß-adrenergic receptors.
In this study, we examined whether increased ß-adrenergic receptor
kinase 1 expression is associated with myocardial
hypertrophy induced by adrenergic stimulation. With use of
implanted mini-osmotic pumps, we treated mice with isoproterenol,
phenylephrine, or vehicle to distinguish between
1- and ß-adrenergic stimulation. Both treatments
resulted in cardiac hypertrophy, but only isoproterenol
induced significant increases in ß-adrenergic receptor kinase-1
protein levels and activity. Similarly, in isolated adult rat cardiac
myocytes, 24 hours of isoproterenol stimulation resulted in a
significant 2.8-fold increase in ß-adrenergic receptor kinase-1
protein levels, whereas 24 hours of phenylephrine treatment
did not alter ß-adrenergic receptor kinase-1 expression. Our results
indicate that increased ß-adrenergic receptor kinase-1 is not
invariably associated with myocardial hypertrophy but
apparently is controlled by the state of ß-adrenergic receptor
activation.
Key Words: myocardial hypertrophy • ß-adrenergic receptor • G protein–coupled receptor kinases • desensitization • catecholamines
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