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(Hypertension. 2001;38:255.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Cardiac ßARK1 Upregulation Induced by Chronic Salt Deprivation in Rats

Guido Iaccarino; Emanuele Barbato; Ersilia Cipolleta; Antonio Esposito; Antonia Fiorillo; Walter J. Koch; Bruno Trimarco

From the Dipartimento di Medicina Clinica e Scienze Cardiovascolari, Federico II University of Naples (G.I., E.B., E.C., A.E., A.F., B.T.), Naples, Italy; and the Department of Surgery, Duke University Medical Center (W.J.K.), Durham, NC.

Correspondence to Guido Iaccarino, MD, PhD, Dipartimento di Medicina Clinica e Scienze Cardiovascolari, Federico II University, Via Pansini 5, 80131 Naples, Italy. E-mail guiaccar{at}unina.it

Abstract— The ß-adrenergic receptor (ßAR) kinase (ßARK1) is a G protein-coupled receptor kinase (GRK) that controls cardiac ßAR signaling via receptor phosphorylation, leading to desensitization. We have observed in mice that chronic isoproterenol administration results in increased myocardial levels of ßARK1 activity, suggesting that adrenergic activation can regulate cardiac ßARK1 expression. Thus, we evaluated left ventricular (LV) ßARK1 levels and activity in response to 3 weeks of a low-sodium (0.05%) diet, which is known to chronically activate the sympathetic nervous system. Wistar-Kyoto rats were subjected to either low or regular sodium (2%) intake. To prove the association of ßARK1 expression and low sodium-induced adrenergic activation, a group of rats was subjected to atenolol treatment (1 mg/kg per day) during the low-sodium diet. LV ßARK1 expression was assessed by protein immunoblotting and ßARK1 activity by in vitro GRK phosphorylation assays. We verified the LV protein levels of GRK5, which is abundantly expressed in the heart. A low-sodium diet reduced body weight and cardiac size so that the heart-to-body weight ratio did not change. On the contrary, low-sodium diet increased by 50% both LV ßARK1 protein (densitometry units: normal sodium, 26.5±0.9; low sodium, 35.7±1.6; P<0.05) and activity (fmol/mg per minute: normal sodium, 6.49±1.17; low sodium, 9.15±0.93; P<0.05). Atenolol treatment prevented the increase in both protein expression (low sodium plus atenolol, 27.6±5.33, P=NS versus normal sodium) and activity (6.54±1.19, P=NS versus normal sodium). GRK5 expression was not affected by a low-sodium diet (17.2±0.2 versus 18.4±0.4, P=NS). Our data indicate that cardiac ßARK1 is regulated by sympathetic action on ßARs as tested by reducing dietary salt and ßAR blockade.

Key Words: G proteins • kinases • receptors, adrenergic, beta • heart • rats • signal transduction • diet

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