Behjat Seifi1, Mehri Kadkhodaee2, Enayatollah Bakhshi3, Mina Ranjbaran2, Maryam Zahmatkesh4, Zahra Sedaghat5, Parisa Ahghari6, Parvaneh Esmaeili7. 1. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: b-seifi@tums.ac.ir. 2. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. 4. Department of Neurosciences and Addiction, School of Advanced in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Physiology and Pharmacology, Medical School, Bushehr University of Medical Sciences, Bushehr, Iran. 6. Department of Physiology, International Campus, Tehran University of Medical Sciences, Tehran, Iran. 7. Research Department, EqlimDanesh Co. Ltd, Tehran, Iran.
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 μg); 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 pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3 ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished 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.
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 IIAT1 receptor antagonist, losartan (0.3 μg); 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 pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3 ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished 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.