Abstract
While the presence of oxidative stress in chronic kidney disease (CKD) is well established, its relation to hypertensive renal hemodynamics remains unclear. We hypothesized that once CKD is established blood pressure and renal vascular resistance (RVR) no longer depend on reactive oxygen species. CKD was induced by bilateral ablation of 2/3 of each kidney. Compared to age-matched, sham-operated controls all ablated rats showed proteinuria, decreased glomerular filtration rate (GFR), more renal damage, higher mean arterial pressure (MAP), RVR and excretion of oxidative stress markers and hydrogen peroxide, while excretion of stable nitric oxide (NO) metabolites tended to decrease. We compared MAP, RVR, GFR and fractional excretion of sodium under baseline and during acute Tempol, PEG-catalase or vehicle infusion in rats with established CKD vs. controls. Tempol caused marked reduction in MAP in controls (96±5 vs.79±4 mmHg, P<0.05) but not in CKD (130±5 vs. 127±6 mmHg). PEG-catalase reduced MAP in both groups (controls: 102±2 vs. 94±4 mmHg, P<0.05; CKD: 118±4 vs. 110±4 mmHg, P<0.05), but did not normalize MAP in CKD rats. Tempol and PEG-catalase slightly decreased RVR in both groups. Fractional excretion of sodium was increased by both Tempol and PEG-catalase in both groups. PEG-catalase decreased TBARS excretion in both groups. In sum, although oxidative stress markers were increased, MAP and RVR did not depend more on oxidative stress in CKD than in controls. Therefore reactive oxygen species appear not to be important direct determinants of hypertensive renal hemodynamics in this model of established CKD.
Highlights
Chronic kidney disease (CKD) is associated with hypertension
Ablation of 2/3 of each kidney leads to established CKD In the CKD group, 3 of the initial 21 animals died during follow-up which resulted in n = 18 of CKD animals, an 85% survival rate
Markers of oxidative stress were increased in CKD: TBARS and 8-isoprostane excretion were significantly higher (P, 0.01 and P,0.001 respectively), whereas H2O2 excretion tended to increase (P = 0.07) vs. control rats were sham-operated (CON) rats (Fig. 1)
Summary
Chronic kidney disease (CKD) is associated with hypertension. Patients with mild to moderate renal insufficiency have increased levels of oxidative stress [1,2,3,4,5] i.e. unfavourable redox balance in which pro-oxidants gain the upper hand over anti-oxidants. This results in a net increase in reactive oxygen species (ROS), leading to cellular and tissue damage. Several studies support the hypothesis that antioxidants may play an important role in the pathogenesis of chronic renal failure and that antioxidant intervention can slow the progression of renal insufficiency in different experimental models of renal disease [8]. With the notable exception of a single study in hemodialysis patients [9], clinical studies showed no beneficial effects of antioxidants in the CKD population [8,10,11]
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