Effects of a didpeptidyl peptidase-4 inhibitor on urinary sodium and water excretion in rats with water-salt disbalance

Abstract

The gastrointestinal tract secretes multiple peptides that regulate metabolic processes and, in particular, influence the kidney function and water-salt balance. The effects of these biologically active substances on carbohydrate metabolism can be intensified by increasing their half-life through inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme. The aim of the study was investigation of sodium and water excretion after inhibition of DPP-4 with vildagliptin in rats with different states of the water-salt balance. Methods. The hypernatremic, hyperosmotic and hypoosmotic states were modeled by oral administration of hypertonic and isotonic NaCl solutions or water. Results. Vildagliptin induced a dose-dependent decrease in the DPP-4 activity with a maximum effect of 1 mg per 100 g of body weight. Vildagliptin administration prior to the hypertonic sodium load increased sodium excretion by 56% and stimulated reabsorption of solute-free and sodium-free water. Administration of the DPP-4 inhibitor before the isotonic sodium load increased sodium excretion to the same degree without affecting the water reabsorption. A vildagliptin injection prior to the water load resulted in an antidiuretic response of the kidneys. Conclusion. The inhibition of DPP-4 activity with vildagliptin promoted removal of excessive sodium from the body and changed the water reabsorption depending on the sodium concentration in the blood serum, presumably by prolonging circulation of the intestinal regulatory peptides secreted in response to oral NaCl load tests. These processes accelerate restoration of the water-salt homeostasis in the conditions of excessive sodium delivery through the gastrointestinal tract.