Effect of Losartan injection into paraventricular nucleus on the deleterious effects of angiotensin II in renal ischemia-reperfusion injury

Introduction: The aim of this study was to investigate the effect of angiotensin II (Ang II) and losartan injections into paraventricular nucleus (PVN) on renal ischemia-reperfusion injury. Methods: After right nephrectomy in male rats, a cannula was inserted into the right PVN. One week later, renal ischemia-reperfusion (IR) injury was induced by clamping the left renal artery for 45 min, and then the kidney was reperfused for 24 h. An Ang II AT1 receptor antagonist, losartan (0.3 μg) was injected into the PVN 20 minutes before the induction of ischemia, followed by 3 ng of Ang II after 10 minutes. Blood, urine and kidney samples in addition to the brain area containing the PVN were collected to evaluate different indices. Renal sympathetic nerve activity (RSNA) was recorded in all groups. Results: Angiotensin II injection into PVN caused significant increases in renal functional (plasma creatinine and BUN as well as urinary NAG activity) and histological indices in comparison to IR group (p<0.05). Losartan injection before Ang II into PVN significantly reduced these markers (p<0.05). In addition, angiotensin II caused significant increases in oxidative stress in PVN (higher MDA and lower SOD) and RSNA compared to the IR group (p<0.05). Losartan improved these markers significantly (p<0.05). Conclusion: This study showed that Ang II injection into PVN increases oxidative stress in PVN and renal sympathetic nerve activity through AT1 receptors and exaggerates renal ischemia-reperfusion injury.