Key result
Microinjection of PEG-SOD into the paraventricular nucleus significantly reduced the capsaicin-induced renal sympathetic nerve activity change from 20.1% to 5.3% in rats.
Absolute Event Rate: 5.3% vs 20.1%
p-value: p=<0.01
In a rat model, NAD(P)H oxidase-derived superoxide anions in the paraventricular nucleus modulate the adipose afferent reflex, providing insight into mechanisms of sympathetic activation.
Hypothesis-generating for PVN superoxide in sympathetic control in rats; leaves open translation to human disease.
BACKGROUND: Adipose afferent reflex (AAR) is a sympatho-excitatory reflex induced by chemical stimulation of white adipose tissue (WAT). Ionotropic glutamate receptors including NMDA receptors (NMDAR) and non-NMDA receptors (non-NMDAR) in paraventricular nucleus (PVN) mediate the AAR. Enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate the role and mechanism of superoxide anions in PVN in modulating the AAR. METHODOLOGY/PRINCIPAL FINDINGS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injections of capsaicin into four sites of right inguinal WAT (8.0 nmol in 8.0 µl for each site). Microinjection of polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide anion scavenger tempol or the NAD(P)H oxidase inhibitor apocynin into the PVN decreased the baseline RSNA and MAP, and attenuated the AAR. Unilateral WAT injection of capsaicin increased superoxide anions in bilateral PVN, which was prevented by the WAT denervation. WAT injection of capsaicin increased superoxide anion level and NAD(P)H oxidase activity in the PVN, which was abolished by the PVN pretreatment with the combined NMDAR antagonist AP5 and non-NMDAR antagonist CNQX. Microinjection of the NMDAR agonist NMDA or the non-NMDAR agonist AMPA increased superoxide anion level and NAD(P)H oxidase activity in the PVN. CONCLUSIONS: NAD(P)H oxidase-derived superoxide anions in the PVN contributes to the tonic modulation of AAR. Activation of ionotropic glutamate receptors in the PVN is involved in the AAR-induced production of superoxide anions in the PVN.
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Ding et al. (2013) studied Adipose afferent reflex and sympathetic activity (n=132). PEG-SOD (polyethylene glycol-superoxide dismutase) vs. Saline was evaluated on Capsaicin-induced renal sympathetic nerve activity (RSNA) change (%) (p=<0.01). Microinjection of PEG-SOD into the paraventricular nucleus significantly reduced the capsaicin-induced renal sympathetic nerve activity change from 20.1% to 5.3% in rats.
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