CNS Gαi2 proteins participate in the central neural regulation of sodium and water homeostasis and in countering salt‐sensitive hypertension

Abstract

HypothesisCentral Gαi2‐protein gated pathways mediate the renal sympathoinhibitory, natriuretic and diuretic responses to acute volume expansion (VE) and counter the development of salt‐sensitive hypertension.MethodsSprague‐Dawley rats were pre‐treated (24h) intracerebroventricularly (i.c.v.) with a scrambled (S) or Gαi2 oligodeoxynucleotide (ODN; 25 μg). Changes in renal sympathetic nerve activity (RSNA), natriuresis and diuresis evoked by acute i.v. isotonic saline VE (5% body weight) were examined. In chronic studies rats were fed normal 0.4% (NS) or high 8% (HS) NaCl chow for 21‐days and brain Gαi2 protein levels were determined (N=6/gp). Separate rats were maintained on NS or HS and infused i.c.v. with a Gαi2 or S ODN, after 21‐days MAP and renal function were assessed (N=4/gp).ResultsCentral Gαi2‐protein down‐regulation attenuated the renal sympathoinhibitory (peak ΔRSNA [% control] S 43±3 vs. Gαi2 88±8, P<0.05 N=4), natriuretic (peak ΔUNaV [μeq/min] S 40±3 vs. Gαi2 26±3, P<0.05 N=6) and diuretic (peak ΔUV [μl/min] S 309±12 vs. Gαi2 225±26, P<0.05 N=6) responses to i.v. VE. In chronic studies HS intake selectively increased Gαi2 protein levels (5.8 fold, P<0.05) in the PVN. When infused with i.c.v. Gαi2 ODN, rats maintained on HS (but not NS) retained sodium (24h Na balance [meq/day] NS + Gαi2 0.3±.0.1 vs. HS + Gαi2 2.75±0.4, P<0.05), retained water (24h H2O balance [ml/day]; NS + Gαi2 12.6±1.3 vs. HS + Gαi2 29.4±3.6, P<0.05) and developed hypertension (MAP [mmHg]; NS + Gαi2 129±2 vs. HS + Gαi2 147±3, P<0.05).ConclusionThese data demonstrate that central Gαi2‐protein gated pathways contribute to the renal sympathoinhibitory and natriuretic responses to acute VE and participate in maintaining sodium and water homeostasis and normotension during high salt challenge. AHA 2250585, DK43337, HL071212, AHA 0855293E, P20 RR018766