Renal Ischemia-reperfusion Leads to Hypertension and Changes in Proximal Tubule Na Transport and Renin-angiotensin-aldosterone System: Role of NADPH Oxidase

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.