TABLE 3

Response of indices of oxidative stress to prolonged tempol administration Mean values are shown.

Model Control Model Tempol Route of Delivery and Duration n Tempol Maximum Dose or Dose Used to Compare Groups ROS Marker and Value in Hypertensive Group without Tempol Control ROS Value in Normotensive Group ROS Value in Hypertensive Group with Tempol Change in ROS Normalization of ROS Reference
%
Studies in hypertensive rat models ACTH [0.2 (mg · kg)/d s.c.] Vehicle p.o. (4 d before to 8 d after ACTH) 10 1 mM Plasma 8-iso, 12.9 nM 8.4 4 d pre, 16.3 8 d post, 13.2 +26/+2 8-iso d 4/8 (NS/NS) –26/–2 Zhang et al., 2003b
   Aldosterone (0.75 μg/h s.c. + salt 1% for 6 wk) Vehicle p.o. for 6 wk 8 3 mM Renal cortex TBARS, 0.23 nmol/mg protein 0.10 0.11 –52* 92 Nishiyama et al., 2004a
Urine TBARS, 0.39 μmol/d 0.10 0.13 –67* 90
   Aldosterone (0.75 μg/h s.c. for 6 wk) Vehicle p.o. for 6 wk 7 1 mM Plasma 8-iso, 16.8 ng/ml 13.1 10.6 –37* 166 Iglarz et al., 2004
NADPH-generated Embedded Image in heart/aorta/kidney/mesenteric artery, 230/930/1500/670 cpm/mg tissue 122/300/250/150 78/340/250/200 –66*/–63*/–83*/70* 141/94/100/90
   Ang II [5 (ng · kg)/min i.v. for 15 d] Vehicle p.o. for 15 d 6 1 mM Plasma/renal vein 8-iso, 193/353 pg/ml 122/202 122/242 –37*/–31* 100/74 Ortiz et al., 2001a
Plasma/renal vein TBARS, 1.7/1.9 nmol/ml 0.8/0.7 1.2/1.1 –33*/–36* 56/67
   Ang II [100 (ng · kg)/min s.c. ± 8% salt for 12 d] Vehicle p.o. for 12 d 5 1 mM Plasma cholesterol ester hydroperoxide levels, 0.27 μM 0.13 0.13 –52* 100 Ogihara et al., 2002
   Ang II [200 (ng · kg)/min s.c. for 2 wk] Vehicle s.c. for 2 wk 8–11 200 (nmol · kg)/min Kidney cortex NADPH oxidase activity, 3.6 nmol of Embedded Image/(min · mg protein) 2.3 2.7 –15* 69 Welch et al., 2005a
   Ang II [300 (ng · kg)/min s.c. for 7 d] Vehicle p.o. for 7 d 8 2 mM Aortic Embedded Image, 4.3 RLU 0.7 1.3 –70* 83 Hattori et al., 2005
   BSO (30 mM for 2 wk) Vehicle p.o. for 2 wk 8 1 mM Urine 8-Iso/Cr, 1.2 pg/mg 0.80 0.82 –33* 98 Banday et al., 2007a
   BSO (30 + HS) HS p.o. for 12 d 8 1 mM Urine 8-Iso/Cr, 1.3 pg/mg 0.84 0.86 –34* 96 Banday et al., 2007c
   Capsaicin-4% salt 4% salt p.o. (gavage) for 3 wk 5–6 1 (mmol · kg)/d Mesenteric artery Embedded Image, 1125 cpm/mg tissue 730 950 –16* 44 Song et al., 2004
   Cyclosporine [30 (mg · kg)/d s.c.] Vehicle p.o. for 3 wk 7 3 mM Kidney TBARS, 37 nmol/g 24 19 –49* 138 Nishiyama et al., 2003
Aortic Embedded Image, 26 cpm 17 16 –38* 111
   DETC [7.5 (mg · kg)/d into medullary interstitium; SD] Tempol only, no DETC Infused into medullary interstitium for 8 d before and during DETC 8 58 (μmol · kg)/d Urine 8-iso, 8.8 ng/d 4.1 ng/d 4.2 ng/d –52* 98 Makino et al., 2003
   Dexamethasone [10 μg · kg)/d s.c.] Vehicle p.o. (4 d before to 8 d after Dex) 10 1 mM Plasma 8-iso, 12 mM 8.8 4 d before, 10.4 –13/17, d 4/8 (NS/NS) 50/63 Zhang et al., 2004b
8 d after, 10
DOCA + salt 0.9% Sham p.o. for 3 wk 6 1 mM Aortic Embedded Image, 3166 (mU · mg)/min 875 824 –74* 102 Ghosh et al., 2004 2004
   DOCA + salt SD/sham high salt i.p. for 3 wk 8 87 (μmol · kg)/d Plasma 8-iso, 0.77 ng/ml 0.20 0.36 –53* 72 Adeagbo et al., 2003
   DOCA + salt 1% Sham p.o. for 4 wk 10 1 mM Embedded Image aortic rings, 7153 cpm/mg tissue 3055 2939 –59* 103 Beswick et al., 2001
   DOCA + salt 1% Sham p.o. for 5 wk 13 1 mM Aortic Embedded Image, 1250 RLU/(min · mg) 525 750 –40* 69 Nakano et al., 2003
   DSS + 8% salt DSR p.o. for 10 wk 9 3 mM Plasma TBARS, 14 nmol/ml 7 7 –50* 100 Guo et al., 2006
Cardiac NADPH oxidase, 361 cpm/mg protein 245 185 –49* 152
   DSS + 8% salt DSS LS p.o. for 5 wk 5 10 mM 8-OHdG-positive cells, 347 cells/area 159 259 –25* 47 Hisaki et al., 2005
   DSS + 8% salt DSS LS p.o. for 4 wk 8 3 mM Urine TBARS, 0.66 μmol/d 0.14 0.24 –64* 81 Kobori and Nishiyama, 2004
   DSS + 8% salt DSS LS p.o. for 2 wk 9 1 mM Urine 8-iso, 14 ng/d 7.4 8 –43* 91 Hoagland et al., 2003
   DSS + 8% salt DSS LS p.o. for 4 wk 8 3 mM Kidney TBARS, 86 nmol/g 41 48 –46* 88 Nishiyama et al., 2004b
   DSS + 8% salt + l-NAME DSS LS p.o. for 2 wk 9 1 mM Urine 8-iso, 15.2 ng/d 7.4 7.5 –51* 99 Hoagland et al., 2003
   DSS + 8% salt + HET-0016 (20-HETE blocker) DSS LS p.o. for 2 wk 9 1 mM Urine 8-iso, 14.6 ng/d 7.4 8.5 –42* 85 Hoagland et al., 2003
   DSS + salt DSS LS i.v. for 3 wk 7 3 (mmol · kg)/d Renal cortical/medullary Embedded Image, 72/35 cpm/mg protein 47/26 22/12 –69*/–66* 200/256 Meng et al., 2003
   ET-1 [5 (pmol · kg)/min i.v. + 8% salt] Vehicle-infused, normal salt p.o. for 12 d 7–10 1 mM Plasma 8-iso, 128 pg/ml 52 72 –44* 74 Elmarakby et al., 2005
Aortic Embedded Image, 740 cpm/mg 90 210 –72* 82
   ET-1 [5 (pmol · kg)/min i.v. + 8% salt] Untreated s.c. for 12 d 7–10 170 (μmol · kg)/d Aortic Embedded Image, 740 cpm/mg 90 240 –68* 77 Elmarakby et al., 2005
   ET-1 [5 (pmol · kg)/min i.v.] Vehicle-infused i.v. for 9 d 6 170 (μmol · kg)/d Kidney TBARS, 462 ng/μg of protein 48 287 –38 (N.S.) 42 (N.S.) Sedeek et al., 2003
Urine 8-iso, 11 ng/d 7.5 8.9 –19* 60
   ET-B antagonist (A-192621) p.o. Vehicle-treated p.o. for 1 wk 6 1 mM Plasma 8-iso, 25 pg/ml 18 23 –8 (N.S.) 29 Williams et al., 2004
Urine H2O2, 4 nmol d <1 <1 –75* 100
   ET-B antagonist + 10% salt p.o. Vehicle-treated p.o. for 1 wk 6 1 mM Plasma 8-iso d 3/7, 75/66 pg/ml 18 57/66 –24/0 (NS/NS) 32/0 Williams et al., 2004
   ET-B deficient + 8% salt Wild type; 8% NaCl p.o. for 15 d 20 1 mM Urine TBARS, 1164 nmol/24 h 1314 1169 –11* 11 Sullivan et al., 2006
   High salt 10% Normal salt p.o. for 1 wk 6 1 mM Plasma 8-iso d 3/7, –64/50 pg/ml 18 60/63 –6/+26 (NS/NS) 9/26 Williams et al., 2004
Urine H2O2, 3 nmol/d <1 2 –33* 50
   Hyperthyroid (s.c. T4 for 6 wk) Vehicle infused p.o. for 6 wk 8 1 mM Plasma MDA, 10.2 μM 6.8 7.5 –26* 79 Moreno et al., 2005
Urine 8-iso, 12.5 μg/d 6.5 7.5 –40* 83
   1K,1C Sham uninephrectomized p.o. for 2 wk 2 d 6 2 mM Aortic Embedded Image, 80 (RLU 15 min/mg) 42 63 –21* 45 Dobrian et al., 2001
Renal nitrotyrosine, 59 ng/mg of protein 14 32 –46* 60
Plasma 8-iso, 240 pg/ml 305 340 –42* 0
   1K,1C (10 wk) Sham p.o. for 5 wk 5 1 mM DHE fluorescence in mesenteric arteries 16 25 –38* 68 Christensen et al., 2007b
   2K,1C Sham s.c. minipump for 13 d 8 288 (μmol · kg)/d Urine 8-iso, 12.5 ng/d 8 9 –28* 78 Welch et al., 2003
Urine MDA, 610 μmol/d 400 330 –46* 133
   Leptin Leptin untreated p.o. for 7 d 8 2 mM Urine 8-iso, 325 ng/d 190 225 –31* 43 Beltowski et al., 2005
Plasma 8-iso, 218 pg/ml 130 138 –37* 91
   Obese Zucker Lean p.o. for 15 d 10 1 mM Renal MDA, 0.91 nmol/mg 0.55 0.59 –35* 89 Banday et al., 2005
   Offspring of protein malnourished mothers Offspring of normal mothers p.o. for 13 wk 14–19 2 mM Kidney nitrotyrosine, 1.42 (relative abundance) 1.0 0.45 –70* 100 Stewart et al., 2005
   Ren-2 transgenic rat Control p.o. for 3 wk 6 1 mM Cardiac MDA, 0.60 μm/mg of protein 47 0.33 –45* 207 Whaley-Connell et al., 2007
   Ren-2 transgenic rat SD p.o. for 3 wk 6 1 mM NADPH oxidase of mesenteric arteries, 18 11 13 –28* 71 Whaley-Connell et al., 2007
   SD + HS (1% NaCl) + BSO (30 mM for 12 d] HS p.o. for 12 d 8 1 mM Urine 8-iso, 54 pg/mg Cr 41 42 –22* 92 Banday et al., 2007d
   SHR WKY s.c. for 2 wk 6–8 200 (nmol · kg)/min Urine 8-iso, 13.2 ng/d N.A. 9.6 –27* N.A. Welch et al., 2005b
   SHR Untreated SHR p.o. for 2 wk 6–8 1 mM Kidney cortex Embedded Image, 11,889 RLU N.A. 9315 –22* N.A. Yanes et al., 2005
Medulla, 6413 RLU 5944 (N.S.) –7 (N.S.)
Plasma total anti-oxidant, 1.2 nM 1.57 –31*
Urine 8-iso, 2.21 ng/mg of creatinine 1.53 –31*
   SHR WKY p.o. for 15 wk 6–12 170 (μmol · kg)/d Kidney 8-iso, 5.2 ng/mg of tissue 1.7 1.7 –67* 100 Fortepiani and Reckelhoff, 2005
   SHR WKY p.o. for 6 wk 6–12 170 (μmol · kg)/d Kidney 8-iso, 5.3 ng/mg of tissue 1.7 4.8 –9* 14 Fortepiani and Reckelhoff, 2005
   SHR WKY p.o. for 2 wk 8 1 mM Urine 8-iso, 9.8 ng/d 6.8 6.0 –39* 127 Schnackenberg and Wilcox, 1999
   SHR aging (16 mo) Untreated SHR p.o. for 8 mo 6 6 mM Urine 8-iso, 20 ng/d N.A. 12 –40* NA Fortepiani et al., 2003
SHR aging female (16 mo) Untreated SHR female p.o. for 8 mo 6 6 mM Urine 8-iso, 45 ng/d N.A. 37 –18* N.A. Fortepiani et al., 2003
   SHR aging (16 mo) Untreated SHR p.o. for 8 mo 10 1 mM Urine 8-iso, 1.84 (ng · mg Cr)/d N.A. 1.28 –30* N.A. Payne et al., 2003
   SHR female WKY p.o. for 15 wk 6–12 170 (μmol · kg)/d Kidney 8-iso, 3.7 ng/mg of tissue 2.2 1.7 –54* 133 Fortepiani and Reckelhoff, 2005
   SHR female WKY p.o. for 6 wk 6–12 170 (μmol · kg)/d Kidney 8-iso, 3.6 ng/mg of tissue 2.2 3.7 +3 (N.S.) 0 Fortepiani and Reckelhoff, 2005
   SHR + l-NAME Untreated SHR p.o. for 2 wk 6–8 1 mM Kidney cortex Embedded Image, 10,423 RLU N.A. 9506 –9* N.A. Yanes et al., 2005
Medulla, 7422 RLU 5248 –29*
Plasma total antioxidant, 1.25 nM 1.46 –17*
Urine 8-iso, 1.89 ng/mg creatinine 1.32 –30*
   SHRsp low Mg2+ diet Untreated SHRsp p.o. for 7 wk 6 1 mM Plasma TBARS, 2.7 μmol/ml N.A. 1.5 –44* N.A. Touyz et al., 2002
Vascular Embedded Image, 1.2 (nmol · min)/mg tissue 0.6 –50*
   SHRsp 4% salt Untreated SHRsp p.o. for 6 wk 6 1 mM Vascular Embedded Image, 19 RLU N.A. 4 –79* N.A. Park et al., 2002
Plasma total antioxidants, 0.85 nM 1.1 +29*
   Streptozotocin (DM)/l-NAME SD, tempol untreated i.v. for 2 wk 5 18 (μmol · kg)/h Urine 8-iso, 118 ng/d 23 40 –66* 82 Brands et al.,
Studies in hypertensive mouse models
   Ang II [0.7 (mg · kg)/d], WT mice Vehicle s.c. for 2 wk 28 (mmol · kg)/d Aortic Embedded Image, 125 pmol/mg of tissue 50 85 –32* 53 Dikalova et al., 2005
Ang II infused [0.7 (mg · kg)/d] Nox-1-overexpressing mice Vehicle s.c. for 2 wk 28 (mmol · kg)/d Aortic Embedded Image, 250 pmol/mg of tissue 75 160 –36* 51 Dikalova et al., 2005

  • 8-iso, 8-isoprostane PGF2α; TBARS, thiobarbituric acid reactive agent; RLU, relative light unit; HS, high salt; Dex, dexamethasone; DSR, Dahl salt-resistant rat; LS, low salt; 8OHdG, 8-hydroxy-2′-deoxyguanosine; HET-0016, N-hydroxy-N′-(4-butyl-2-methylphenyl)-formamidine; N.A., not applicable; adrenocorticotropin; d, day(s); wk, week(s); mo, month(s)

  • ↵* Significant change with tempol