NADPH oxidase inhibition reduces tubular Na+ transport and improves kidney oxygenation in diabetic rats

Abstract

Sustained hyperglycemia is associated with increased oxidative stress and decreased renal oxygen tension (pO2) secondary to increased oxygen consumption. The NADPH oxidase is a major source of oxygen radicals in the kidney and we therefore studied the effects of NADPH oxidase inhibition (apocynin; APO) on tubular Na+ transport and kidney pO2 in diabetic rats. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; transonic flow probe), proximal tubular electrolyte transport (Li+ clearance) and tissue pO2 (microelectrodes) were measured in Inactin-anesthetized control and streptozotocin-diabetic rats during baseline and after acute APO administration (10 mg/kg bolus). Diabetic rats had increased GFR (2.2±0.3 vs. 1.4±0.1 ml/min/kidney), reduced pO2 in cortex and medulla (34.6±0.9 & 15.7±1.2 vs. 41.6±1.9 & 26.1±2.3 mmHg), increased Na+ excretion (24.0±4.7 vs. 9.0±2.0 μm/h/kidney) and reduced Li+ excretion compared to controls (0.23±0.02 vs. 0.38±0.06). RBF was similar in both groups. In diabetics, APO increased Na+ (156%) and Li+ excretion (48%) and improved renal pO2 (21–35%), whereas GFR and RBF were unchanged. All parameters were unaffected by APO administered to control animals. Type-1 diabetic patients have increased risk to develop salt-sensitive hypertension, and our findings may provide a mechanistic explanation for this phenomenon.