Abstract
BackgroundInflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension.MethodsPrehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively.ResultsNLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3.ConclusionsSalt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.
Highlights
Inflammation has been implicated in the development of cardiovascular disease
The expression of nod-like receptor with pyrin domain containing 3 (NLRP3)/apoptosisassociated speck-like protein (ASC)/IL-1β in the paraventricular nucleus (PVN) of high-salt diet rats by the second month In this study, we found that NLRP3, ASC, and IL-1β expressions in the PVN of high-salt diet increased significantly by the second month, with a corresponding increase in the blood pressure
Blockade NLRP3 suppression of ASC/pro-caspase-1/IL-1β expression in PVN of high-salt diet rats To determine whether suppression of NLRP3 in PVN attenuates inflammation response, we examined the protein level of NLRP3 pathway in PVN
Summary
We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. Recent evidences have associated hypertension with a chronic low-grade systemic inflammation [1].The most susceptible among all organs to increased blood pressure is the brain [2]. Growing body of evidence have demonstrated that increased pro-inflammatory cytokines (PICs) within PVN play an important role in the progression of hypertension [4, 5]. The role of intracellular NOD like receptors, such as pyrin domain containing 3 (NLRP3) in hypertension remains unknown. In this study, we analyze the role of NLRP3, PICs, chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), and neurohormone level in the development of prehypertension
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