Excess dietary salt intake is an established cause of @entity101 . At present, our understanding of the neuropathophysiology of salt-sensitive @entity101 is limited by a lack of identification of the central nervous system mechanisms that modulate sympathetic outflow and blood pressure in response to dietary salt intake. We hypothesized that impairment of brain Gai2-protein-gated signal transduction pathways would result in increased sympathetically mediated renal @entity1372 retention, thus promoting the development of salt-sensitive @entity101 . To test this hypothesis, naive or renal denervated Dahl salt-resistant and @entity1702 ( @entity1702 ) @entity35 were assigned to receive a continuous intracerebroventricular control scrambled or a targeted Gai2-oligodeoxynucleotide infusion, and naive Brown Norway and 8-congenic @entity1702 @entity35 were fed a 21-day normal or high-salt diet. High salt intake did not alter blood pressure, suppressed plasma @entity1063 , and evoked a site-specific increase in hypothalamic paraventricular nucleus Gai2-protein levels in naive Brown Norway, Dahl salt-resistant, and scrambled oligodeoxynucleotide-infused Dahl salt-resistant but not @entity1702 @entity35 . In Dahl salt-resistant @entity35 , Gai2 downregulation evoked rapid renal nerve-dependent @entity101 , @entity1372 retention, and sympathoexcitation. In @entity1702 @entity35 , Gai2 downregulation exacerbated salt-sensitive @entity101 via a renal nerve-dependent mechanism. Congenic-8 @entity1702 @entity35 exhibited @entity1372 -evoked paraventricular nucleus-specific Gai2-protein upregulation and attenuated @entity101 , @entity1372 retention, and global sympathoexcitation compared with @entity1702 @entity35 . These data demonstrate that paraventricular nucleus Gai2-protein-gated pathways represent a conserved central molecular pathway mediating sympathoinhibitory renal nerve-dependent responses evoked to maintain @entity1372 homeostasis and a salt-resistant phenotype. Impairment of this mechanism contributes to the development of salt-sensitive @entity101 .

Gai2-protein-mediated signal transduction: central nervous system molecular mechanism countering the development of XXXX -dependent @entity101 .

@entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity1702 :: ('MESH:D013651', 'Disease') :: ['DSS', 'Dahl salt-sensitive'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine']
@entity1372 :: (MESH:D012964,Chemical) :: ['sodium']
