Reactive oxygen species in paraventricular nucleus modulates cardiac sympathetic afferent reflex in rats

Han, Ying; Zhang, Ying; Wang, Han Jun; Gao, Xing-Ya; Wang, Wei; Zhu, Guo‐Qing

doi:10.1016/j.brainres.2005.07.055

Cited by 50 publications

(70 citation statements)

References 34 publications

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“…Because ICV Ang II infusion resulted in an increase in MSAP under the condition of UCP2 upregulation in RVLM, oxidative stress in other areas of brain may also participate in central Ang II-induced hypertension. In this regard, oxidative stress in the subfornical 34 and hypothalamic areas 35 in the forebrain also contributes to neural mechanism of Ang II-induced hypertension.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension

Chan

et al. 2009

Circulation Research

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Rationale: Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production. Objective: We assessed the hypothesis that UCP2 participates in central cardiovascular regulation by maintaining reactive oxygen species homeostasis in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that maintain vasomotor tone located. We also elucidated the molecular mechanisms that underlie transcriptional upregulation of UCP2 in response to oxidative stress in RVLM. Key Words: uncoupling proteins Ⅲ mitochondrion Ⅲ peroxisome proliferator-activated receptor Ⅲ oxidative stress Ⅲ blood pressure L iving organisms possess a variety of physiological protective mechanisms to counteract oxidative stress and to restore redox balance. Oxidative damage to cells that results from an imbalance of production over degradation of the reactive oxygen species (ROS), particularly superoxide anion (O 2 Ϫ⅐ ) and hydrogen peroxide (H 2 O 2 ), is associated with a variety of cardiovascular diseases, including heart failure, atherosclerosis, and hypertension. 1-3 Of note is that overproduction of O 2 Ϫ⅐ and H 2 O 2 in the central nervous system contributes to neural mechanisms of hypertension by increasing sympathetic outflow to the peripheral blood vessels. 4,5 In addition to the degradative enzymes (eg, superoxide dismutase [SOD] and catalase) and low-molecular-weight antioxidants (eg, ascorbic acid and glutathione), the uncoupling proteins (UCPs) have emerged as important natural antioxidants in the maintenance of ROS homeostasis. 6 UCPs belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation by causing proton leakage across the mitochondrial inner membrane, leading to energy dissipation and heat production. 7 More importantly, the resultant decrease in proton electrochemical gradient across the inner mitochondrial membrane elicited by the UCPs mitigates mitochondrial ROS production. 6,8 In mammals, 5 homologues, UCP1 to UCP5, have so far been cloned. 9 Among them, dysfunction of UCP2 is suggested to be of considerable importance in cardiovas- Methods and Results

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Section: Discussionmentioning

confidence: 99%

Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension

Chan

et al. 2009

Circulation Research

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“…It was reported that AT 1 receptors are densely distributed in the PVN [3,28]. Our previous studies indicated that angiotensin II (Ang II) and AT 1 receptors in the PVN played important roles in the central modulation of CSAR and contributed to the pathogenesis of enhanced CSAR in CHF [16,27,[30][31][32][33].…”

Section: Introductionmentioning

confidence: 98%

“…We recently reported that reduced-form nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase-derived reactive oxygen species (ROS) especially superoxide anions in the PVN mediated the CSAR and contributed to the effect of Ang II in the PVN on the CSAR in rats [16,30]. It is known that superoxide anions are quickly converted to hydrogen peroxide (H 2 O 2 ) by superoxide dismutase (SOD).…”

Section: Introductionmentioning

confidence: 99%

Endogenous hydrogen peroxide in paraventricular nucleus mediating cardiac sympathetic afferent reflex and regulating sympathetic activity

Zhong

et al. 2007

Pflugers Arch - Eur J Physiol

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We previously reported that reactive oxygen species (ROS) in paraventricular nucleus (PVN) mediated cardiac sympathetic afferent reflex (CSAR). The present study investigated the role of endogenous hydrogen peroxide (H(2)O(2)), a ROS, in the PVN in mediating the CSAR and regulating sympathetic activity. The CSAR was evaluated by the response of renal sympathetic nerve activity (RSNA) to epicardial application of bradykinin (BK) in rats. Bilateral microinjection of polyethylene glycol-catalase (PEG-CAT, an analogue of endogenous catalase) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) into the PVN abolished the CSAR, decreased baseline RSNA and mean arterial pressure (MAP). Moreover, pretreatment with PEG-CAT or PEG-SOD blocked the enhanced CSAR and RSNA responses induced by exogenous angiotensin II (Ang II) in the PVN. Aminotriazole (ATZ, a catalase inhibitor) alone potentiated the CSAR, increased RSNA and MAP, but failed to augment the Ang II-induced CSAR enhancement responses. Pretreated with PEG-SOD, ATZ still increased baseline RSNA and MAP but inhibited the CSAR and Ang II-induced CSAR and RSNA enhancement responses. These results suggested that endogenous H(2)O(2) in the PVN mediated both the CSAR and Ang II-induced CSAR enhancement responses. H(2)O(2) in the PVN were involved in regulating sympathetic activity and arterial pressure.

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“…Superoxide anion scavenger tempol in the PVN abolished the effects of Ang II on the CSAR and RSNA [13]. The NAD(P)H oxidase-derived superoxide anions in the PVN mediate the CSAR and is involved in Ang II-induced CSAR-enhancing effect in the PVN in normal rats [29] and chronic heart failure rats [12].…”

Section: Discussionmentioning

confidence: 97%

c-Src in paraventricular nucleus modulates sympathetic activity and cardiac sympathetic afferent reflex in renovascular hypertensive rats

Han

Yuan

Zhang

et al. 2011

Pflugers Arch - Eur J Physiol

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Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. The study was to determine whether c-Src in paraventricular nucleus (PVN) is involved in the enhanced CSAR and sympathetic activation in hypertensive rats induced by two-kidney one-clip (2K1C). At the end of the fourth week after 2K1C surgery, renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats with baroreceptor denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. In the PVN, c-Src activity was higher in 2K1C rats than sham-operated (Sham) rats while c-Src expression was not. Epicardial application of capsaicin or PVN microinjection of angiotensin II (Ang II) increased c-Src activity more in 2K1C than Sham rats. PVN microinjection of selective Src family kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazol [3,4-D] pyrimidine (PP2) or 2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H-indol-2-yl)methylene]-1 H-indole-5-sulfonamide (SU6656) abolished the CSAR and decreased RSNA more in 2K1C than Sham rats. The Ang II-induced RSNA and CSAR enhancement was abolished by PP2 or SU6656 pretreatment in 2K1C and Sham rats. NAD(P)H oxidase activity and superoxide anion level in PVN were higher in 2K1C rats, which was attenuated by PP2 but increased by epicardial application of capsaicin or PVN microinjection of Ang II. The effects of capsaicin or Ang II were abolished by PP2. These results indicate that c-Src in the PVN is involved in the enhanced CSAR and sympathetic activation in renovascular hypertension, and mediates the excitatory effects of Ang II in the PVN on the CSAR and sympathetic activity via NAD(P)H oxidase-derived generation of superoxide anions.

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Reactive oxygen species in paraventricular nucleus modulates cardiac sympathetic afferent reflex in rats

Cited by 50 publications

References 34 publications

Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension

Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension

Endogenous hydrogen peroxide in paraventricular nucleus mediating cardiac sympathetic afferent reflex and regulating sympathetic activity

c-Src in paraventricular nucleus modulates sympathetic activity and cardiac sympathetic afferent reflex in renovascular hypertensive rats

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