Renal ischemia-reperfusion leads to hypertension and changes in proximal tubule Na+ transport and renin-angiotensin-aldosterone system: Role of NADPH oxidase

• Published in: Life sciences (1973) Vol. 266; p. 118879
• Main Authors: Lima, Natália K.S., Farias, Wilka R.A., Cirilo, Marry A.S., Oliveira, Angélica G., Farias, Juliane S., Aires, Regina S., Muzi-Filho, Humberto, Paixão, Ana D.O., Vieira, Leucio D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2021; Elsevier BV
• Subjects: Acute kidney injury; Acute Kidney Injury - complications; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Aldosterone; Aldosterone - metabolism; Angiotensin; Angiotensin II; Animals; Blood pressure; Drinking water; Hypertension; Hypertension - enzymology; Hypertension - etiology; Hypertension - pathology; Ischemia; Ischemia-reperfusion; Isoforms; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - pathology; Kinases; Lipid peroxidation; Lipids; Male; Na+/K+-exchanging ATPase; NAD(P)H oxidase; NADPH oxidase; NADPH Oxidases - metabolism; Oxidase; Oxidative Stress; Peptidyl-dipeptidase A; Peroxidation; Protein kinase C; Rats; Rats, Wistar; Receptors; Renal cortex; Renin; Renin-Angiotensin System; Renin-angiotensin-aldosterone system; Reperfusion; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Risk analysis; Risk factors; Sodium; Sodium - metabolism; Surgery; Hypertension; Ischemia-reperfusion; Renin-angiotensin-aldosterone system; Acute kidney injury; NADPH oxidase
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118879

Acute renal injury (AKI) is a risk factor for the development of hypertension, which involves oxidative stress, changes in Na+ handling, and the intrarenal renin-angiotensin-aldosterone system (RAAS) as underlying mechanisms. We investigated in rats whether renal ischemia-reperfusion (IR) leads to changes in the proximal tubule ATP-dependent Na+ transport and the intrarenal content of RAAS components, as well as the role of NADPH oxidase. Rats weighing 300–350 g were submitted to AKI by bilateral IR (n = 25). After IR injury, the animals were followed up for 4 weeks. One part (n = 7) received daily treatment with the NADPH oxidase inhibitor apocynin (100 mg/kg, drinking water), while another part (n = 9) received apocynin 24 h before and after IR. One group was submitted to sham surgery (n = 8). Four weeks after IR, the rats presented elevated systolic blood pressure, as well as increased lipid peroxidation, NADPH oxidase activity, (Na++K+)ATPase activity, and upregulation of type 1 angiotensin II receptor in the renal cortex. On the other hand, there was a decrease in Na+-ATPase activity and downregulation of the isoforms 1 and 2 of the angiotensin-converting enzyme, type 2 angiotensin II receptor, and of the α and ε isoforms of protein kinase C. Most of these alterations was prevented by both apocynin treatment protocols. Thus, we conclude that AKI-induced by IR may induce changes in proximal tubule ATPases and RAAS components compatible with renal Na+ retention and hypertension. These data also indicate that the NADPH oxidase represents a key factor in the origin of these alterations.