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

Recent studies indicate that systemic administration of tumor necrosis factor (TNF)-α induces increases in corticotrophin releasing hormone (CRH) and CRH type 1 receptors in the hypothalamic paraventricular nucleus (PVN). In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague-Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the increases in RSNA, ACTH and PVN glutamate, NE and TH observed in HF rats. These findings suggest that CRH in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced HF.

TNF-α in hypothalamic paraventricular nucleus contributes to sympathoexcitation in heart failure by modulating AT1 receptor and neurotransmitters.

Proinflammatory cytokines, including tumor necrosis factor (TNF)-α, augment the progression of heart failure (HF) that is characterized by sympathoexcitation. In this study, we explored the role of TNF-α in hypothalamic paraventricular nucleus (PVN) in the exaggerated sympathetic activity observed in HF. Heart failure rats were made by ligating the left anterior descending coronary artery. The expression levels of angiotensin type 1 receptor (AT1-R) and neurotransmitters were analyzed in the PVN of HF rats that received direct PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle. Sham-operated control (SHAM) or HF rats were treated for 4 weeks through PVN infusion with each TNF-α blocker or vehicle. Rats with HF had higher levels of glutamate, norepinephrine, AT1-R and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA), neuronal nitric oxide synthase (nNOS) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, norepinephrine and angiotensin II and renal sympathetic nerve activity (RSNA) were increased in HF rats. PVN infusion of pentoxifylline or etanercept attenuated the decreases in PVN GABA, nNOS and GAD67, and the increases in RSNA and PVN glutamate, norepinephrine, TH and AT1-R observed in HF rats. We have developed a novel method for chronic and continuous infusion of drugs directly into the PVN and provided evidence that TNF-α in the PVN modulates neurotransmitters and the expression of AT1 receptor, which could account for exaggerated sympathetic activity in HF.

[Near infrared determination of dry hay quality in oats].

In the present paper, the analysis of the content of CP, NDF and ADF in the whole dry hay of oats was carried out by using near infrared reflectance spectroscopy (NIRS) technique, and in combination with the partial least square (PLS) regression algorithm the calibration analysis was performed at the same time. The results showed that the calibration models developed by the spectral data pretreatment of the second derivative + Norris smoothing, the multivariate scattering correction + second derivative + Norris smoothing, and the multivariate scattering correction were the best for CP, NDF and ADF with the same spectral regions (9668-4518, 9550-5543, 8943-4042 cm(-1)). All these models yielded coefficients of determination of calibration (r2 cal) for CP and NDF that are both higher than 0.95, and each error lower than 3%, approached the chemical analysis precision. Moreover, the values of (RPD) of CP and NDF were both higher than 3.0. The results of these studies indicate that the contents of CP and NDF can be used to measure various samples in screening and evaluating quality constituents of dry hay in oats. While the effect of ADF modelling was poorer, the coefficients of determination of calibration (r2 cal) and cross validation (r2 CV)for ADF were 0.9120, 0.8553 respectively. The root mean square error of calibration, root mean square error of cross validation, and root mean square error of prediction ( RMSEE, RMSECV and RMSEP) for ADF were 2.33%, 2.62% and 1.91% respectively, and the precision is near the precision of the chemical analysis. The models of ADF can be used to measure various samples in screening and evaluating quality constituents of dry hay of oats also. This study has proved that NIRS technique can be applied to detect the contents of CP, NDF and ADF in the whole dry hay of oats.

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

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-1ß) 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-1ß 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-1ß, 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-1ß activation in the PVN plays a role in salt-sensitive hypertension.

Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus.

High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1ß, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1ß, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension.