Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats

Figures

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  Fig. 1. A representative picture of microinjection sites in the PVN evaluated by Evans blue (50 nL) diffusion (a); the effect of HFD on the values of systolic blood pressure (SBP) and the plasma levels of norepinephrine (NE) and TNFα (b–d for each group, n = 7); and the relative values of TNFα protein expression and mRNA levels in the PVN (e, f for each group, n = 4–5). The values are mean ± SD.*p < 0.05 versus Control. Arrows indicate the microinjection sites. PVN paraventricular nucleus, 3V the third ventricle, OH obesity-related hypertension. SBP was measured under conscious state

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  Fig. 2. The effects of PVN microinjection of saline and TNFα (0.5 ng or 1 ng) on the baseline RSNA and MAP (a, b), and TNFα (1 ng) caused SNA response (the changes of RSNA and MAP) to the pretreatment of TNFα receptor antagonist R-7050 in the PVN. The values are mean ± SD. For each group, n = 6–7; *p < 0.05 versus saline (a, b); #p < 0.05 versus Control (a, b); &p < 0.05 versus TNFα (0.5 ng a, b); *p < 0.05 versus Saline + Saline (c, d); &p < 0.05 versus Control (c, d); #p < 0.05 versus Saline + TNFα (c, d). RSNA renal sympathetic nerve activity, MAP mean artery pressure

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  Fig. 3. Representative recordings of the capsicin (CAP)-induced AAR are shown by the RSNA and MAP responses to the application of TNFα (1 ng) in the PVN in rats (a, b); the effect of PVN microinjection of saline and TNFα (0.5 ng or 1 ng) into the PVN on the AAR (c, d). The values are mean ± SD. For each group, n = 6; *p < 0.05 versus Saline; #p < 0.05 versus Control; &p < 0.05 versus TNFα (0.5 ng). AAR adipose afferent reflex

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  Fig. 4. The effects of saline, R-7050 (TNFα receptor antagonist), DETC (superoxide dismutase inhibitor), PEG-SOD (superoxide scavenger) and Apo (NADPH oxidase inhibitor) pretreatment in the PVN on the AAR response to TNFα in the PVN. TNFα (1 ng) was administered 10 min after the pretreatment. The values are mean ± SD. For each group, n = 6–7; *p < 0.05 versus Saline + Saline; #p < 0.05 versus Saline + TNFα (1 ng); &p < 0.05 versus Control

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  Fig. 5. The effects of R-7050 pretreatment on the NADPH oxiase activity (f), ROS level (e) and the in situ ROS content (a–d) responses to TNFα in the PVN. In situ ROS was determined with a specific fluorogenic probe by the DHE method (n = 3 for each group). The NADPH oxiase activity was detected by the enhanced lucigenin chemiluminescence method and the ROS level were measured by the lucigenin-derived chemiluminescence method (n = 6 for each group). The values are mean ± SD; *p < 0.05 versus Control + Saline + Saline; #p < 0.05 versus OH + Saline + Saline; &p < 0.05 versus OH + Saline + TNFα. PVN paraventricular nucleus, 3V the third ventricle

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  Fig. 6. The effects of chronic systemic application of pentoxifylline (PTX, a cytokine blocker, 30 mg/kg, IP) for 5 weeks on the AAR (a, b), systolic blood pressure (c) and plasma norepinephrine levels (d) (n = 6–7 for each group) in rats. Values are mean ± SD. *p < 0.05 versus Control; #p < 0.05 versus OH

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  Fig. 7. The effects of chronic systemic application of pentoxifylline (PTX, a cytokine blocker, 30 mg/kg, IP) for 5 weeks on the in situ ROS (n = 3 for each group, a–d), ROS level (n = 6–7 for each group, f), protein expression of TNFα in the PVN (n = 3–4 for each group, g) and TNFα content in plasma (n = 6–7 for each group, e). The values are mean ± SD; *p < 0.05 versus Control; #p < 0.05 versus OH

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  Fig. 8. The effects of chronic systemic application of pentoxifylline (PTX, a cytokine blocker, 30 mg/kg, IP) for 5 weeks on the mRNA (a, b) and protein (c, d) expressions of the NOX2 and NOX4 isoforms of NADPH oxidase. The values are mean ± SD; *p < 0.05 versus Control; #p < 0.05 versus OH