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Role of Vasopressin in the Regulation of Renal Sodium Excretion: Interaction with Glucagon‐Like Peptide‐1
Author(s) -
Kutina A. V.,
Golosova D. V.,
Marina A. S.,
Shakhmatova E. I.,
Natochin Y. V.
Publication year - 2016
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12367
Subject(s) - endocrinology , medicine , natriuresis , vasopressin , chemistry , reabsorption , sodium , exenatide , agonist , excretion , glucagon like peptide 1 , receptor , kidney , type 2 diabetes , diabetes mellitus , organic chemistry
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 V 2 receptors (51.6 ± 3.7 μmol/min/kg, P < 0.05) and was reduced by a V 1a 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 V 1a agonist (1 μg/kg) induced an increase in sodium fractional excretion to 10 ± 2% and 8 ± 2%, respectively. Combined administration of exenatide and V 1a 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.