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.