The present study aimed to investigate the potential physiological role of vasopressin and the incretin hormone of the gastrointestinal tract (glucagon-like peptide-1; GLP-1) in the regulation of the water-salt balance in a hyperosmolar state as a result of sodium loadings. In rats, the administration of hypertonic NaCl solution resulted in a significant increase in natriuresis, which correlated with the vasopressin excretion rate. Natriuresis following an i.p. NaCl load (23.2 ± 1.4 μmol/min/kg) was enhanced by inhibition of V2 receptors (51.6 ± 3.7 μmol/min/kg, P < 0.05) and was reduced by a V1a antagonist injection (6.3 ± 1.1 μmol/min/kg, P < 0.05). Compared to i.p. salt administration, oral NaCl loading induced a significant increase in the plasma GLP-1 level within 5 min and resulted in more prominent natriuresis and a smaller increase in blood sodium concentration. It was hypothesised that the basis for the fast elimination of excess sodium following an oral NaCl load could be the involvement of GLP-1 in osmoregulation combined with vasopressin. It was demonstrated that GLP-1 mimetic exenatide (1.5 nmol/kg) produced a significant decrease in proximal reabsorption and an increase in fractional sodium excretion (from 0.15 ± 0.04% to 9 ± 1%). It was also shown that vasopressin at doses of 1-10 μg/kg and the selective V1a agonist (1 μg/kg) induced an increase in sodium fractional excretion to 10 ± 2% and 8 ± 2%, respectively. Combined administration of exenatide and V1a agonist revealed their cumulative natriuretic effect, and sodium fractional excretion increased by up to 18 ± 2%. These data suggest that GLP-1 combined with vasopressin could be involved in the regulation of sodium balance in the hyperosmolar state as a result of NaCl loading. Vasopressin regulates the reabsorption of a significant portion of filtered sodium in the distal segment of the nephron and modulates the natriuretic effect of GLP-1.
Keywords: GLP-1; V1a receptor; V2 receptor; natriuresis; vasopressin.
© 2016 British Society for Neuroendocrinology.