Cardiac betaARK1 upregulation induced by chronic salt deprivation in rats.

The beta-adrenergic receptor (betaAR) kinase (betaARK1) is a G protein-coupled receptor kinase (GRK) that controls cardiac betaAR signaling via receptor phosphorylation, leading to desensitization. We have observed in mice that chronic isoproterenol administration results in increased myocardial levels of betaARK1 activity, suggesting that adrenergic activation can regulate cardiac betaARK1 expression. Thus, we evaluated left ventricular (LV) betaARK1 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 betaARK1 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 betaARK1 expression was assessed by protein immunoblotting and betaARK1 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 betaARK1 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 betaARK1 is regulated by sympathetic action on betaARs as tested by reducing dietary salt and betaAR blockade.