title: Brain Gαi2-subunit protein-gated pathways are required to mediate the centrally evoked sympathoinhibitory mechanisms activated to maintain sodium homeostasis.
abstract: OBJECTIVE
  We have previously demonstrated a role of GPCR-activated brain Gαi(2)-subunit protein-gated pathways in the natriuretic responses evoked by exogenous central α(2)-adrenoceptor activation and acute intravenous (i.v.) volume expansion in vivo. Our objective was to examine the role of brain Gαi(2) proteins in the integrated neural-humoral responses evoked by i.v. isovolumetric sodium loading, which does not alter mean arterial blood pressure or total blood volume, to maintain sodium homeostasis in conscious Sprague-Dawley rats.
  
  
  METHODS
  Intact or chronic bilateral renal denervated (RDNX) rats were pretreated intracerebroventricularly (i.c.v.) with a scrambled or Gαi(2) oligodeoxynucleotide to selectively downregulate brain Gαi(2) proteins. On the day of study, an i.v. isovolumetric sodium load (1 mol/l NaCl) was administered.
  
  
  RESULTS
  In naive and scrambled oligodeoxynucleotide groups, i.v. sodium loading evoked profound natriuresis, suppression of plasma renin activity (PRA) and global sympathoinhibition. Prior downregulation of brain Gαi(2) proteins significantly attenuated the natriuretic response [peak ΔUNaV (μeq/μl); scrambled 22 ± 2 vs. Gαi(2) 13 ± 2, P < 0.05] and abolished the sympathoinhibitory response [peak Δplasma norepinephrine (% control); SCR -72 ± 8 vs. Gαi(2) -7 ± 5, P < 0.05] without attenuating PRA suppression to sodium loading. In RDNX rats, Gαi(2) oligodeoxynucleotide pretreatment failed to attenuate the natriuretic response [peak ΔUNaV (μeq/μl); RDNX and scrambled 19 ± 3 vs. RDNX and Gαi(2) 20 ± 2] and only partially prevented the sympathoinhibitory response to i.v. sodium loading.
  
  
  CONCLUSIONS
  These studies reveal a brain Gαi(2)-subunit protein-mediated (renin-angiotensin system-independent) sympathoinhibitory pathway that has a critical role in the central neural mechanisms activated to maintain fluid and electrolyte homeostasis.
authors: Department of Pharmacology and Experimental Therapeutics and the Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. rwainf@bu.edu
authors: Richard D
authors: RD
authors: Wainford
authors: Crissey L
authors: CL
authors: Pascale
authors: Jill T
authors: JT
authors: Kuwabara
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012964:Sodium / Q000008:administration & dosage / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D017931:DNA Primers; D012964:Sodium; D012083:Renin; D051960:GTP-Binding Protein alpha Subunit, Gi2; D009638:Norepinephrine