Renovascular effects of inorganic nitrate following ischemia-reperfusion of the kidney.

Redox biology 2021 Feb

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Renal ischemia-reperfusion (IR) injury is a common cause of acute kidney injury (AKI), which is associated with oxidative stress and reduced nitric oxide (NO) bioactivity and increased risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD). New strategies that restore redox balance may have therapeutic implications during AKI and associated complications. To investigate the therapeutic value of boosting the nitrate-nitrite-NO pathway during development of IR-induced renal and cardiovascular dysfunction. Male C57BL/6 J mice were given sodium nitrate (10 mg/kg, i. p) or vehicle 2 h prior to warm ischemia of the left kidney (45 min) followed by sodium nitrate supplementation in the drinking water (1 mmol/kg/day) for the following 2 weeks. Blood pressure and glomerular filtration rate were measured and blood and kidneys were collected and used for biochemical and histological analyses as well as renal vessel reactivity studies. Glomerular endothelial cells exposed to hypoxia-reoxygenation, with or without angiotensin II, were used for mechanistic studies. IR was associated with reduced renal function and slightly elevated blood pressure, in combination with renal injuries, inflammation, endothelial dysfunction, increased Ang II levels and Ang II-mediated vasoreactivity, which were all ameliorated by nitrate. Moreover, treatment with nitrate (in vivo) and nitrite (in vitro) restored NO bioactivity and reduced mitochondrial oxidative stress and injuries. Acute treatment with inorganic nitrate prior to renal ischemia may serve as a novel therapeutic approach to prevent AKI and CKD and associated risk of developing cardiovascular dysfunction. Copyright © 2020. Published by Elsevier B.V.

Citation

Gensheng Zhang, Huirong Han, Zhengbing Zhuge, Fang Dong, Shan Jiang, Wenwen Wang, Drielle D Guimarães, Tomas A Schiffer, En Yin Lai, Lucas Rannier Ribeiro Antonino Carvalho, Ricardo Barbosa Lucena, Valdir A Braga, Eddie Weitzberg, Jon O Lundberg, Mattias Carlstrom. Renovascular effects of inorganic nitrate following ischemia-reperfusion of the kidney. Redox biology. 2021 Feb;39:101836