Peripheral vs central administration of NaCl differently modulates vasopressin secretion through the regulation of PVN Gαq sub‐unit proteins

Abstract

HypothesisPVN Gαq sub‐unit protein gated pathways, which are stimulatory on AVP secretion, are endogenously down‐regulated to prevent excess AVP secretion following peripheral, but not central, administration of NaCl.MethodsSprague‐Dawley rats were maintained on 0.4% or 8% NaCl chow, or were infused intracerebroventricularly (i.c.v.) with aCSF or 0.8M NaCl aCSF for 21‐days (N=5/gp). PVN tissue was examined for Gαz & Gαq protein expression (normalized to GAPDH) via immunoblotting. Plasma AVP levels were determined via ELISA. In rats treated chronically as described above, N/OFQ (peptide inhibitor of AVP) was injected i.c.v. (5.5 nmol) and urine output was collected for 90‐min (10‐min periods). Separate rats infused with 0.8M NaCl (21‐days) were pre‐treated i.c.v. with a Gαq oligodeoxynucleotide (ODN; 25 μg) 24‐h prior to plasma AVP and PVN Gαz/q protein measurement.Results 0.4% NaCl diet 8% NaCl diet aCSF i.c.v. infusion 0.8M NaCl aCSF i.c.v. infusion 0.8M NaCl aCSF i.c.v. infusion + Gαq ODN PVN Gαq Protein levels [ODU] 0.99±0.07 0.12±0.05* 1.16±0.06 1.09±0.08 0.22±0.04# PVN Gαz Protein levels [ODU] 2.24±0.13 2.34±0.12 2.01±0.12 2.12±0.13 2.08±0.11 AVP [pg/ml] 1.39±0.07 1.38±0.14 1.50±0.17 2.12±0.17# 0.99±0.06# Peak Diuresis to N/OFQ [μl/min] 199±16 191±11 177±23 54±12# T.B.D. *, # Sig diff vs 0.4% NaCl or aCSF gp;ConclusionIn response to a peripheral salt load, which does not elevate CSF NaCl levels, the down‐regulation of PVN Gαq proteins is an endogenous counter regulatory mechanism to prevent salt‐induced increases in plasma AVP levels and water retention. When CSF NaCl is increased, this counter‐regulatory mechanism fails, leading to increased circulating AVP and an impaired diuretic ability. AHA 2250585, DK43337, HL071212, AHA 0855293E, P20 RR018766