Chronic activation of β-adrenergic receptors leads to tissue water and electrolyte retention.

β-Adrenergic receptors (β-ARs) are expressed on the membranes of various cell types, and their activation affects body water balance by modulating renal sodium and water excretion, cardiovascular function, and metabolic processes. However, β-AR-associated body fluid imbalance has not been well characterized. In the present study, we hypothesized that chronic β-AR stimulation increases electrolyte and water content at the tissue level. We evaluated the effects of isoproterenol, a nonselective β-AR agonist, on electrolyte and water balance at the tissue level. Continuous isoproterenol administration for 14 days induced cardiac hypertrophy, associated with sodium-driven water retention in the heart; increased the total body sodium, potassium, and water contents at the tissue level; and increased the water intake and blood pressure of mice. There was greater urine output in response to the isoproterenol-induced body water retention. These isoproterenol-induced changes were reduced by propranolol, a nonselective β receptor inhibitor. Isoproterenol-treated mice, even without excessive water intake, had higher total body electrolyte and water contents, and this tissue water retention was associated with lower dry body mass, suggesting that β-AR stimulation in the absence of excess water intake induces catabolism and water retention. These findings suggest that β-AR activation induces tissue sodium and potassium retention, leading to body fluid retention, with or without excess water intake. This characterization of β-AR-induced electrolyte and fluid abnormalities improves our understanding of the pharmacological effects of β-AR inhibitors. SIGNIFICANCE STATEMENT: This study has shown that chronic β-adrenergic receptor (β-AR) stimulation causes cardiac hypertrophy associated with sodium-driven water retention in the heart and increases the accumulation of body sodium, potassium, and water at the tissue level. This characterization of the β-AR-induced abnormalities in electrolyte and water balance at the tissue level improves our understanding of the roles of β-AR in physiology and pathophysiology and the pharmacological effects of β-AR inhibitors.