title: Superoxide dismutase mimetic, tempol, aggravates renal injury in advanced-stage stroke-prone spontaneously hypertensive rats.
abstract: OBJECTIVE
  The aim of this study was to determine whether antioxidant therapy could relieve hypertension and retard the progression of renal damage in advanced-stage hypertensive rats.
  
  
  METHODS
  Twenty-four-week-old spontaneously hypertensive stroke-prone rats were treated for 8 weeks with the superoxide dismutase mimetic tempol, low-dose or high-dose candesartan (an angiotensin receptor blocker), or hydralazine, and blood pressure and renal damage were compared.
  
  
  RESULTS
  Elevated blood pressure and renal damage with heterogeneity were present after 8 weeks, with greater glomerulosclerosis in the juxtamedullary glomeruli than in the superficial glomeruli. Although both tempol and candesartan effectively reduced reactive oxygen species production in the kidney, tempol did not decrease blood pressure and exacerbated urine protein and histological damage, such as glomerulosclerosis and interstitial fibrosis, particularly in juxtamedullary nephrons (tempol vs. untreated: glomerulosclerosis index, 2.0 vs. 1.5, P<0.01; fibrosis, 15 vs. 10%, P<0.001). In contrast, high-dose candesartan and hydralazine prevented these forms of renal damage with lowering blood pressure. Low-dose candesartan also prevented this renal damage without lowering blood pressure. Moreover, there were increased numbers of larger and smaller glomeruli in the juxtamedullary cortex of tempol-treated rats, suggesting that changes in glomerular hemodynamics may be responsible for the exacerbation of glomerulosclerosis. Both candesartan- and hydralazine-treated rats had glomeruli that were slightly decreased in size.
  
  
  CONCLUSIONS
  These results suggest that single-antioxidant therapy starting at an advanced-stage may be ineffective for hypertension and rather exacerbate renal damage in nonsalt loaded SHRSP. Furthermore, lowering blood pressure and inhibiting the renin-angiotensin system could be critical for slowing the progression of hypertensive renal damage at an advanced stage.
authors.affiliation: Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus School of Medicine, Okinawa, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sugama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kohagura
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamazato
authors.forename: Takuto
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shinzato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohya
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000633:toxicity*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D018716:Molecular Mimicry; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism*; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013777:Tetrazoles; D006830:Hydralazine; D013482:Superoxide Dismutase; C081643:candesartan; C001803:tempol