Superoxide Anions in Paraventricular Nucleus Modulate Adipose Afferent Reflex and Sympathetic Activity in Rats

Abstract

BackgroundAdipose 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 FindingsRenal 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.ConclusionsNAD(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.

Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats

“…, Ding et al . ). Furthermore, PVN participated in the regulation of enhanced AAR in rats with obesity and obesity‐related hypertension (Xiong et al .…”

Neural Control of Non-vasomotor Organs in Hypertension

“…This may be particularly relevant for the growing epidemic of obesity-induced hypertension as it is becoming evident that CNS pathways/factors that are classically involved in sympathetic cardiovascular control also modulate sympathetic outflow to metabolic organs [94]. Consideration for the mechanisms discussed above, along with additional factors (e.g., insulin, resistin) [96, 97] and reflex pathways (e.g., adipose tissue afferent reflexes) [98] not discussed in this review, will be crucial in this regard. Lastly, it is important to consider regional sympathetic outflow in both hypertensive human and animal models.…”

GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats

“…Bilateral PVN microinjections were carried out with two glass micropipettes (about 50 μm tip diameter) and completed within 1 min. The microinjection volume was 50 nl for each side of the PVN [ 11 ]. The effective doses of chemicals used for the PVN microinjection were based upon previous studies [ 14 , 18 – 21 ].…”

“…Ionotropic glutamate receptors in the PVN mediate the AAR and regulate sympathetic outflow in rats [ 10 ]. The activation of ionotropic glutamate receptors in the PVN is involved in the AAR-induced production of superoxide anions, and NAD(P)H oxidase-derived superoxide anions in the PVN contributes to the tonic modulation of AAR [ 11 ]. Furthermore, activation of melanocortin-4 receptors in the PVN enhances the AAR via a cAMP-PKA pathway [ 12 ].…”