Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure

Self Cite

High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1β and attenuating p-IKKβ, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump. The mean arterial pressure and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of p-IKKβ, NF-κB p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1β, and lower levels of IL-10 in the PVN than normal diet rats. Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These findings suggest that high-salt-induced NF-κB activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1β and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates NLRP3, IL-1β and oxidative stress in the PVN and thereby attenuates hypertension.

Section: Implantation Of Bilateral Pvn Cannulaementioning

confidence: 99%

NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1

Shi

et al. 2015

Self Cite

“…IL-1b is an important proinflammatory cytokine with pleiotropic effect, which involves in a broad spectrum of cellular responses [8,30]. NAD(P)H oxidase is the main producer of reactive oxygen species (ROS) in the PVN and has been shown to be activated and play an important role in both human and animal hypertensive models [17,31,32]. Central IL-1b inhibition reverses alterations in RAS components, reduces production of ROS in the PVN and consequently delays hypertension-induced cardiovascular damage.…”

Section: Discussionmentioning

confidence: 99%

Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats

Zhao

et al. 2015

Self Cite

Findings from our laboratory indicate that expressions of some proinflammatory cytokines such as tumor necrosis factor, interleukin-6 and oxidative stress responses are increased in the hypothalamic paraventricular nucleus (PVN) and contribute to the progression of salt-sensitive hypertension. In this study, we determined whether interleukin-1 beta (IL-1β) activation within the PVN contributes to sympathoexcitation during development of salt-dependent hypertension. Eight-week-old male Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks, and all rats were treated with bilateral PVN injection of gevokizumab (IL-1β inhibitor, 1 μL of 10 μg) or vehicle once a week. The mean arterial pressure (MAP), heart rate (HR) and plasma norepinephrine (NE) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 [subunits of NAD (P) H oxidase], IL-1β, NLRP3 (NOD-like receptor family pyrin domain containing 3), Fra-LI (an indicator of chronic neuronal activation) and lower levels of IL-10 in the PVN than normal-diet rats. Bilateral PVN injection of gevokizumab decreased MAP, HR and NE, attenuated the levels of oxidative stress and restored the balance of cytokines. These findings suggest that IL-1β activation in the PVN plays a role in salt-sensitive hypertension.

“…Immunofluorescence labeling was performed in floating sections as described previously [20][21][22] to identify salusin b expressions. Briefly, rats (n = 6 per group) were anaesthetized by a ketamine (80 mg/kg) and xylazine (10 mg/ kg) mixture (ip).…”

Section: Immunofluorescence Studiesmentioning

confidence: 99%

Salusin β Within the Nucleus Tractus Solitarii Suppresses Blood Pressure Via Inhibiting the Activities of Presympathetic Neurons in the Rostral Ventrolateral Medulla in Spontaneously Hypertensive Rats

Liu

et al. 2015

Self Cite

Salusin β is a newly identified bioactive peptide, which shows peripheral hypotensive, mitogenic and proatherosclerotic effects. The present study was undertaken to investigate the role of salusin β within the nucleus tractus solitarii (NTS) and the underlying mechanism in regulating blood pressure and heart rate (HR) in spontaneously hypertensive rats (SHR). Our results showed that bilateral or unilateral microinjection of salusin β (0.4-40 pmol) into the NTS in SHR decreased mean arterial pressure and HR in a dose-dependent manner. Bilateral microinjection of salusin β (4 pmol) within NTS improved baroreflex sensitivity functions in SHR. Pretreatment with glutamate receptors antagonist kynurenic acid (5 nmol) into the NTS in SHR did not alter the salusin β (4 pmol) induced hypotension and bradycardia. Likewise, bilateral vagotomy also did not alter the salusin β (4 pmol) induced hypotension and bradycardia. However, pretreatment with GABAA receptors agonist muscimol (100 pmol) within the rostral ventrolateral medulla (RVLM) in SHR almost completely abolished the hypotension and bradycardia evoked by intra-NTS salusin β (4 pmol). Our findings suggested that microinjection of salusin β into the NTS produced hypotension and bradycardia, as well as improved baroreflex sensitivity functions, via inhibiting the activities of presympathetic neurons in the RVLM in SHR.