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PVN Gαi 2 protein‐gated signal transduction ‐ a renal nerve dependent mechanism required for sodium homeostasis and blood pressure regulation in Sprague‐Dawley rats
Author(s) -
Wainford Richard David,
Kuwabara Jill Toshiko
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.906.18
Subject(s) - endocrinology , medicine , natriuresis , chemistry , hydrochlorothiazide , plasma renin activity , homeostasis , fractional excretion of sodium , excretion , blood pressure , renin–angiotensin system
Aim We examined the role of PVN Gαi2 proteins, which are upregulated by high salt intake, in maintaining salt‐resistance. Methods Naïve, bilateral renal denervated (RDNX) or sham RDNX Sprague‐Dawley rats (N=6/gp) received a bilateral PVN infusion of a scrambled (S) or Gαi2 oligodeoxynucleotide (ODN‐300ng/side/day) and a 7‐day normal 0.4% (NS) or high 8% NaCl (HS) diet. On day‐7 MAP, 24h Na+ balance, FENa, plasma norepinephrine (NE), plasma renin activity (PRA), urinary angiotensinsogen (UAGT), and natriuresis to i.v. hydrochlorothiazide (HCTZ‐1.5mg/kg) were assessed. Results HS‐intake increased FENa, suppressed plasma NE, PRA, UAGT & natriuresis to HCTZ (P<0.05) without altering MAP in PVN S infused rats. HS intake in intact & sham RDNX rats receiving a PVN Gαi2 infusion evoked elevated plasma NE (NE [nmol/L]; S intact HS 43±4 vs Gαi2 intact HS 108±8, P<0.05), increased natriuresis to HCTZ (peak ΔUNaV to HCTZ [μeq/min]; S intact HS 7.4±0.6 vs Gαi2 intact HS 14.7±0.9, P<0.05), hypertension (MAP [mmHg]; S intact HS 128±2 vs Gαi2 intact HS 147±3, P<0.05), reduced FENa (FENa [%]; S intact HS 0.9±0.1 vs Gαi2 intact HS 0.2±0.1, P<0.05) and suppressed PRA and UAGT. RDNX in HS maintained PVN Gαi2 infused rats prevented hypertension (MAP [mmHg]; Sham RDNX HS Gαi2 149±3 vs RDNX HS Gαi2 132±4, P<0.05), elevated plasma NE, sodium retention and enhanced natriuresis to HCTZ (peak ΔUNaV to HCTZ [μeq/min]; Sham RDNX HS Gαi2 14.8±1 vs RDNX HS Gαi2 8.5±0.7, P<0.05). Conclusion Renal nerve dependent dysregulation of sympathetically driven, but not RAAS mediated, sodium retaining mechanisms, potentially involving altered NCC regulation, occurred following PVN Gαi2‐protein down‐regulation. Therefore PVN Gαi2 protein‐gated pathways represent a central mechanism required to regulate NE mediated sodium homeostasis and maintain salt‐resistance ‐ HL107330.