Inhibition of microglial activation in rats attenuates paraventricular nucleus inflammation in Gαi₂ protein-dependent, salt-sensitive hypertension.

ABSTRACT:

New findings

• What is the central question of this study? We hypothesized that central inflammatory processes that involve activation of microglia and astrocytes contribute to the development of Gαi₂ protein-dependent, salt-sensitive hypertension. • What is the main finding and its importance? The main finding is that PVN-specific inflammatory processes, driven by microglial activation, appear to be linked to the development of Gαi₂ protein-dependent, salt-sensitive hypertension in Sprague-Dawley rats. This finding might reveal new mechanistic targets in the treatment of hypertension.

Abstract

The central mechanisms underlying salt-sensitive hypertension, a significant public health issue, remain to be established. Researchers in our laboratory have reported that hypothalamic paraventricular nucleus (PVN) Gαi₂ proteins mediate the sympathoinhibitory and normotensive responses to high sodium intake in salt-resistant rats. Given the recent evidence of central inflammation in animal models of hypertension, we hypothesized that PVN inflammation contributes to Gαi₂ protein-dependent, salt-sensitive hypertension. Male Sprague-Dawley rats received chronic intracerebroventricular infusions of a targeted Gαi₂ or control scrambled oligodeoxynucleotide (ODN) and were maintained for 7 days on a normal-salt (NS; 0.6% NaCl) or high-salt (HS; 4% NaCl) diet; in subgroups on HS, intracerebroventricular minocycline (microglial inhibitor) was co-infused with ODNs. Radiotelemetry was used in subgroups of rats to measure mean arterial pressure (MAP) chronically. In a separate group of rats, plasma noradrenaline, plasma renin activity, urinary angiotensinogen and mRNA levels of the PVN pro-inflammatory cytokines TNFα, IL-1β and IL-6 and the anti-inflammatory cytokine IL-10 were assessed. In additional groups, immunohistochemistry was performed for markers of PVN and subfornical organ microglial activation and cytokine levels and PVN astrocyte activation. High salt intake evoked salt-sensitive hypertension, increased plasma noradrenaline, PVN pro-inflammatory cytokine mRNA upregulation, anti-inflammatory cytokine mRNA downregulation and PVN-specific microglial activation in rats receiving a targeted Gαi₂ but not scrambled ODN. Minocycline co-infusion significantly attenuated the increase in MAP and abolished the increase in plasma noradrenaline and inflammation in Gαi₂ ODN-infused animals on HS. Our data suggest that central Gαi₂ protein prevents microglial-mediated PVN inflammation and the development of salt-sensitive hypertension.

SUBMITTER: Moreira JD 

PROVIDER: S-EPMC6884700 | biostudies-literature |

REPOSITORIES: biostudies-literature