title: Maintenance of hypertensive hemodynamics does not depend on ROS in established experimental chronic kidney disease.
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.
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Papazova
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arianne
authors.initials: A
authors.lastname: van Koppen
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten P
authors.initials: MP
authors.lastname: Koeners
authors.affiliation: Department of Anatomy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Bleys
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002374:Catalase / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry; D020869:Gene Expression Profiling; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006861:Hydrogen Peroxide / Q000737:chemistry; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C001803:tempol