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A novel CNS Gαi 2 protein‐gated renal sympathoinhibitory pathway is essential to maintain sodium and water homeostasis in response to isovolumetric sodium loading
Author(s) -
Wainford Richard David
Publication year - 2011
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.25.1_supplement.1079.1
Subject(s) - chemistry , endocrinology , natriuresis , medicine , sodium , isovolumetric contraction , diuresis , diuretic , homeostasis , blood pressure , kidney , organic chemistry , diastole
Hypothesis Central Gαi 2 ‐subunit proteins mediate the centrally evoked sympathoinhibitory, natriuretic and diuretic responses to acute i.v. isovolumetric sodium loading in conscious rats. Methods An isovolumetric sodium load (1M NaCl) was administered over 2h by i.v. infusion (20 μl/min) in conscious naïve or chronic bilateral renal denervated (RDNX) Sprague‐Dawley rats pre‐treated intracerebroventricularly (i.c.v.; 24‐h) with a scrambled (SCR) or Gαi 2 oligodeoxynucleotide (ODN; 25 μg/each; N=6/group). MAP, HR and urine output were recorded for 5‐hrs (1hr control, 2h NaCl load, 2 h recovery). Plasma norepinephrine (NE) content and plasma renin activity (PRA) were measured during control, sodium load and recovery periods. Results In response to an i.v. isovolumetric 1M sodium load, prior down‐regulation of brain Gαi 2 ‐proteins attenuated the natriuresis (peak ΔUNaV [μeq/μl]; SCR 25±3 vs. Gαi 2 ODN 12±2, P<0.05) and diuresis (peak ΔUV [μl/min]; SCR 53±5 vs. Gαi 2 ODN 24±3, P<0.05), and abolished the global sympathoinhibitory response (peak Δplasma NE [% control]; SCR −78±5 vs. Gαi 2 ODN −3±2, P<0.05) without altering the suppression of PRA activity (peak ΔPRA activity [Ang I generation ng/ml/h]; SCR −2.6±0.3 vs. Gαi 2 ODN −2.4±0.2). In contrast, in chronic RDNX rats, Gαi 2 ODN pre‐treatment failed to alter the natriuretic (peak ΔUNaV [μeq/μl]; SCR 20±2 vs. Gαi 2 ODN 21±2) and diuretic responses (peak ΔUV [μl/min]; SCR 45±4 vs. Gαi 2 ODN 44±3) and partially restored the global sympathoinhibitory response to the sodium load (peak Δplasma NE [% control]; SCR −74±6vs. Gαi 2 ODN −44±4, P<0.05). Conclusion We have discovered a novel brain Gαi 2 ‐protein mediated sympathoinhibitory renal nerve dependent (renin‐angiotensin system independent) pathway that has a critical role in the endogenous central neural mechanisms activated to maintain fluid and electrolyte homeostasis. AHA 2250585, NIH P20RR018766.