title: Role of Vasopressin in the Regulation of Renal Sodium Excretion: Interaction with Glucagon-Like Peptide-1.
abstract: 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.
authors.affiliation: Laboratory of Renal Physiology and Water-Salt Balance, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Kutina
authors.affiliation: Laboratory of Renal Physiology and Water-Salt Balance, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Golosova
authors.affiliation: Laboratory of Renal Physiology and Water-Salt Balance, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Marina
authors.affiliation: Laboratory of Renal Physiology and Water-Salt Balance, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
authors.forename: E I
authors.initials: EI
authors.lastname: Shakhmatova
authors.affiliation: Laboratory of Renal Physiology and Water-Salt Balance, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
authors.forename: Y V
authors.initials: YV
authors.lastname: Natochin
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017483:Receptors, Vasopressin / Q000819:agonists; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D012964:Sodium / Q000097:blood / Q000378:metabolism*; D014667:Vasopressins / Q000502:physiology*; D014688:Venoms / Q000494:pharmacology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D010455:Peptides; D017483:Receptors, Vasopressin; D012462:Saline Solution, Hypertonic; C582098:V1a vasopressin receptor, rat; D014688:Venoms; D014667:Vasopressins; D052216:Glucagon-Like Peptide 1; D012964:Sodium; D000077270:Exenatide
keywords: GLP-1; V1a receptor; V2 receptor; natriuresis; vasopressin