Abstract 105: PVN Inflammation Contributes to Brain GαI2 Protein Dependent Sympathetically Mediated Salt Sensitive Hypertension

Abstract

Hypothesis: PVN inflammation contributes to salt sensitive hypertension (HTN) that develops following central Gαi2 protein down regulation. Methods: Male Sprague-Dawley (SD) rats receiving a continuous I.C.V. scrambled (S) or a targeted Gαi2 oligodeoxynucleotide (ODN) infusion (25μg/5μl/day) were fed a normal (NS; 0.6% NaCl) or high salt (HS; 4% NaCl) diet for 7-days (N=4-6/group). Additional groups received a S or Gαi2 ODN and minocycline (120 μg/day) co-infusion and a 7-day HS diet. On day 7 24h sodium balance, MAP, plasma norepinephrine content (via ELISA) and PVN specific mRNA levels of IL1β, IL6, IL10 and TNFα (via RT-PCR) were assessed. Separate groups underwent IHC analysis of PVN astrocytes and PVN microglia activation. Results: Central Gαi2 protein down regulation, but not control S ODN treatment, results in HS evoked HTN, sympathoexcitation, sodium retention, increased PVN mRNA levels of pro-inflammatory cytokines IL1β, IL6 and TNFα, decreased PVN anti-inflammatory 1L10 mRNA levels and no change in astrocyte PVN levels. Significantly, Gαi2 protein down regulation increased PVN microglial activation in rats on a NS diet. I.C.V. minocycline (anti-inflammatory antibiotic) co-infusion abolished the HS-evoked pro-inflammatory mRNA cytokine response and attenuated HTN, sympathoexcitation and sodium retention following central Gαi2 protein down regulation. Conclusion: PVN inflammation contribute to central Gαi2 protein dependent salt sensitive HTN by modulating sympathetic outflow and sodium homeostasis. We speculate central Gαi2 protein downregulation evokes microglial activation to prime a pro-inflammatory PVN response to HS intake.