Renal cortical oxygen tension is decreased following exposure to long-term but not short-term intermittent hypoxia in the rat

Chronic kidney disease (CKD) occurs in more than 50% of patients with obstructive sleep apnea (OSA). However, the impact of intermittent hypoxia (IH) on renal function and oxygen homeostasis is unclear. Male Sprague Dawley rats were exposed to IH (270 secs at 21% O2; 90 secs hypoxia, 6.5% O2 at nadir) for 4 h (AIH) or to chronic IH (CIH) for 8h/day for 2 weeks. Animals were anesthetized and surgically prepared for the measurement of mean arterial pressure (MAP), and left renal excretory function, renal blood flow (RBF), and renal oxygen tension (PO2). AIH had no effect on MAP (123±14 versus (v) 129±14mmHg, mean±SEM, sham v IH). The CIH group were hypertensive (122±9 v 144±15mmHg, P<0.05). Glomerular filtration rate (GFR) (0.92±0.27 v 1.33±0.33ml/min), RBF (3.8±1.5 v 7.2±2.4ml/min) and transported sodium (TNa) (132±39 v 201±47μmol/min) were increased in the AIH group (all P<0.05). In the CIH group, GFR (1.25±0.28 v 0.86±0.28ml/min, P<0.05) and TNa (160±39 v 120±40μmol/min, P<0.05) were decreased, while RBF (4.13±1.5 v 3.08±1.5ml/min) was not significantly different. Oxygen consumption (QO2) was increased in the AIH group (6.76±2.60 v 13.60±7.77μmol/min, P<0.05), but was not significantly altered in the CIH group (3.97±2.63 v 6.82±3.29μmol/min). Cortical PO2 was not significantly different in the AIH group (46±4 v 46±3mmHg), but was decreased in the CIH group (44±5mmHg v 38±2mmHg, P<0.05). AIH: Renal oxygen homeostasis was preserved through a maintained balance between O2 supply (RBF) and consumption (GFR). CIH: Mismatched TNa and QO2 reflects inefficient O2 utilization and thereby sustained decrease in cortical PO2

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in mdx diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease