The role of incretin as an integrator of sodium and water balance regulation.

Abstract

Sodium balance in the body determines the key physiological parameters, such as the volume of extra� cellular fluid and its osmolality. Blood volume affects hemodynamics and blood content of the vessels, and blood plasma osmolality determines the volume of each cell in the body. Despite changes in the supply of Na + salts and the rate of salt excretion by kidneys, intestine and other organs, the Na + balance in humans and mammalians is continuously maintained at a sta� ble level, and it is controlled by the nervous system and endocrine glands. Physiologically active substances affecting Na + excretion by the kidney include aldos� terone (1), atriopeptid (2, 3), prostaglandin Е2 (4-6), etc. We recently demonstrated that incretin, a peptide of the gastrointestinal tract (glucagonlike peptide�1), produced in response to food intake (7), is involved in the regulation of excretion of Na + and free water by the kidney (8-10). The goal of this study was to deter� mine the role of incretins in Na + balance in the cases of alternative types of impairment of Na + balance (hypoand hypernatremia). Usually, some hormones are secreted upon an increase in the content of Na + in the body, and other hormones are secreted when the content of Na + is decreased. Aldosterone enters the blood during hypo� volemia, which means a sodium deficit (1), the secre� tion of atriopeptide into the bloodstream is observed during hypervolemia (2), and vasopressin is secreted during hypovolemia and hyperosmia (11). Based on the above facts, the goal of the present study was to clarify the role of incretin based on the effect of its mimetic during hypervolemia at an unchanged, a decreased or an increased Na + concen� tration in the blood serum. In other words, against a background of an increased volume of extracellular fluid, we estimated the effect of incretin and reaction of the body to differently directed shift of Na + concen� tration in the blood serum. Exenatide, which is more resistant to enzymatic degradation in the blood com� pared with glucagonlike peptide�1 was used as an incretin mimetic (12). Experiments were carried out on female Wistar rats with body weights of 180-230 g. The rats received standard pelleted food (recipe PK�120, Aller Petfood, Russia) and had free access to water. After 5 p.m. in the previous evening and in the morning of the experi� ment, the rats received no food, but they had access to water. At the end of experiment, the rats were returned to their cages in a vivarium and used in repeated exper� iments no earlier than after one week. Animal han� dling and experiments were performed according to Russian and international regulations for the handling of laboratory animals. During the experiment, the rats were placed to individual cages with wire bottoms through which urine could flow via a funnel into a vol� umetric tube.