Angiotensin Ii in Paraventricular Nucleus Contributes to Sympathoexcitation in Renal Ischemia-Reperfusion Injury by At1 Receptor and Oxidative Stress Publisher Pubmed



Seifi B¹ ; Kadkhodaee M¹ ; Bakhshi E² ; Ranjbaran M¹ ; Zahmatkesh M³ ; Sedaghat Z⁴ ; Ahghari P⁵ ; Esmaeili P⁶ Show Affiliations
Source: Journal of Surgical Research Published:2015

Abstract

Background: To investigate the effect of angiotensin II (Ang II) in the hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion (IR) injury and to assay the role of renal sympathetic nerve activity (RSNA). Methods: A cannula was inserted into the right side PVN in Sprague-Dawley rats for microinjection of Ang II (3, 30, and 300 ng); Ang II AT1 receptor antagonist, losartan (0.3 mg); and the superoxide dismutase (SOD) mimetic, tempol (20 nmol) before right side nephrectomy. After 1 wk, renal IR injury was induced by clamping the left renal artery for 45 min, and then reperfusion for 3 or 24 h. The extent of renal damage was determined by evaluation of renal functional indices. RSNA was recorded in all groups. Oxidative stress indices (SOD activity and malondialdehyde levels) were assayed in the PVN. Results: Microinjection of pharmacologicdoses of AngII into the PVNexaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dosedependently. The effects of Ang II (3ng)was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of AngIIonrenal IR injury, RSNA, and oxidative stress we reabolished by pretreatment with tempol. Conclusions: These results indicate that the PVN is a responsive site for central Ang II increment damage in renal ischemia-reperfusion injury. We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by AT1 receptors and oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway. © 2015 Elsevier Inc. All rights reserved.