TABLE 2

Blood pressure response to prolonged tempol administration Mean values are shown for systolic blood pressure (SBP) or mean arterial pressure (MAP) and percent blood pressure response or percentage normalization of blood pressure. Tempol dose p.o. is concentration of tempol in the drinking water unless otherwise noted.

Model Control Model Tempol Route of Delivery and Duration n Tempol Maximum Dose or Dose Used to Compare Groups SBP or MAP BP Response Reference
Control Normotensive Experimental Hypertensive Group without Tempol Experimental Group with Tempol Change Normalization
mm Hg %
Studies in hypertensive rats with systemic tempol
   ACTH (0.2 (mg · kg)/d s.c.) Vehicle p.o. from 4 d before to 8 d after ACTH 10 1 mM 119 134 4 d, 118* 4 d, –12 4 d, 106 Zhang et al., 2003b
8 d, 123 (N.S.) 8 d, –8 8 d, 73
   Aldosterone (0.75 μg/h s.c. + salt 1% for 6 wk) Vehicle p.o. for 6 wk 8 3 mM 118 165 125* –24 85 Nishiyama et al., 2004a
   Aldosterone (0.75 μg/h s.c. for 6 wk) Vehicle p.o. for 6 wk 7 1 mM 123 170 149* –12 45 Iglarz et al., 2004
   Ang II [5 (ng · kg)/min i.v. for 15 d] Vehicle p.o. for 15 d 6 1 mM 119 151 119* –21 100 Ortiz et al., 2001a
   Ang II [100 (ng · kg)/min s.c. ± 8% salt diet for 12 d] Vehicle p.o. for 12 d 5 1 mM 127 184 150* –18 60 Ogihara et al., 2002
   Ang II [200 (ng · kg)/min s.c. for 2 wk] Vehicle s.c. minipump for 2 wk 8–11 200 (nmol · kg)/min 104 146 116* –21 71 Welch et al., 2005a
   Ang II [300 (ng · kg)/min s.c. for 7 d] Vehicle p.o. for 7 d 8 2 mM 125 186 142* –24 72 Hattori et al., 2005
   BSO (30 mM for 2 wk] SD p.o. for 2 wk 8 1 mM 100 123 104* –15 82 Banday et al., 2007a
   BSO (30 mM) + HS for 2 wk HS p.o. for 12 d 8 1 mM 112 143 107* –25 116 Banday et al., 2007c
   Capsaicin-4% salt (WKY) None p.o. (gavage) for 3 wk 5–6 1 (mmol · kg)/d 113 150 150 (N.S.) 0 0 Song et al., 2004
   Cyclosporine [30 (mg · kg)/d s.c.) Vehicle p.o. for 3 wk 7 3 mM 119 145 115* –21 115 Nishiyama et al., 2003
   Dexamethasone [10 (μg · kg)/d s.c.] Vehicle-infused p.o. from 4 d before to 8 d after Dex 10 1 mM 122 136 4 d, 128* 4 d, –6 4 d, 57 Zhang et al., 2004b
8 d, 122* 8 d, –10 8 d, 100
   DOCA-salt Sham p.o. for 3 wk 6 1 mM 107 161 108* –33 100 Ghosh et al., 2004
   DOCA-salt SD/sham-salt i.p. for 3 wk 8 87 (μmol · kg)/d 119 164 123* –25 91 Adeagbo et al., 2003
   DOCA-salt Sham i.p. for 3 wk 8 87 (μmol · kg)/d 130 203 151* –26 71 Awe et al., 2003
   DOCA-salt Sham p.o. for 5 wk 13 1 mM 118 200 176* –12 29 Nakano et al., 2003
   DOCA-salt Sham p.o. for 4 wk 10 1 mM 113 199 142* –29 66 Beswick et al., 2001
   DSS/8% salt DSS LS and DSR p.o. for 10 wk 9 3 mM 120 220 191* –13 29 Guo et al., 2006
   DSS/8% salt DSS LS p.o. for 5 wk 5 10 mM 144 224 186* –17 47 Hisaki et al., 2005
   DSS/8% salt DSS LS p.o. for 4 wk 8 3 mM 107 184 128* –30 73 Kobori and Nishiyama, 2004
   DSS/8% salt DSS/NS p.o. for 3 wk 34 1 mM 148 233 199* –15 40 Bayorh et al., 2006
   DSS + salt DSS LS i.v. for 3 wk 7 3 (mmol · kg)/d 122 140 118* –16 102 Meng et al., 2003
   DSS + 8% NaCl DSS LS p.o. for 4 wk 8 3 mM 113 185 128* –31 79 Nishiyama et al., 2004b
   DSS + 8% NaCl DSR p.o. for 8–10 wk 20 1 mM 124 179 132* –26 85 Ozawa et al., 2004
   ET-1 [5 (pmol · kg)/min]-8% salt Vehicle-treated, normal salt p.o. for 12 d 7–10 1 mM 114 132 127 (N.S.) –4 28 Elmarakby et al., 2005
   ET-1 [5 (pmol · kg)/min]-8% salt Tempol untreated s.c. for 12 d 7–10 170 (μmol · kg)/d 114 138 134 (N.S.) –3 16 Elmarakby et al., 2005
   ET-1 [5 (pmol · kg)/min] i.v. Vehicle-infused i.v. for 9 d 6 170 (μmol · kg)/d 125 141 127* –10 87 Sedeek et al., 2003
   ET-B antagonist (A-192621) p.o. Vehicle-treated p.o. for 1 wk 6 1 mM 100 117 117 (N.S.) 0 0 Williams et al., 2004
   ET-B antagonist-10% salt p.o. Vehicle-treated, 10% salt p.o. for 1 wk 6 1 mM Day 3, 110 Day 3, 135 Day 3, 120* Day 3, –11 Day 3, 60 Williams et al., 2004
Day 7, 110 Day 7, 138 Day 7, 138 (N.S.) Day 7, 0 Day 7, 0
   Fructose-fed Fructose untreated p.o. for 4 wk 7 1 mM 101 128 103* –19 93 Onuma and Nakanishi, 2004
   Hyperthyroid (s.c. thyroxine for 6 wk) Vehicle-infused p.o. for 6 wk 8 1 mM 120 147 127* –14 74 Moreno et al., 2005
   High salt 10% Normal salt p.o. for 1 wk 6 1 mM 98 112 100* –11 85 Williams et al., 2004
   Inducible renin transgene-8% salt Pre-salt loading p.o. for 10 d 6 2 mM 137 171 148* –13 63 Howard et al., 2005
   Intermittent hypoxia (sleep apnea) SD p.o. for 2 wk ? 1 mM 101 118 107* –9 65 Troncoso Brindeiro et al., 2007
   1K,1C Sham UNX p.o. for 2 wk 6 2 mM 95 159 139* –13 31 Dobrian et al., 2001
   1K,1C (10 wk) Sham p.o. for 5 wk 5 1 mM 130 170 135* –21 90 Christensen et al., 2007b
   2K,1C Sham s.c. minipump for 13 d 8 288 (μmol · kg)/d 105 148 118* –20 70 Welch et al., 2003
   Lead (100 ppm for 12 wk) SD without lead in diet i.p. for 2 wk 6 15 (mmol · kg)/d 122 173 143* –17 59 Vaziri et al., 2001
   Leptin Leptin untreated p.o. for 7 d 8 2 mM 126 152 128* –16 92 Beltowski et al., 2005
   Offspring of protein-malnourished mothers Offspring of normal mothers p.o. for 13 wk including 3 wk pre-HTN 14–19 2 mM 130 143 130* –9 100 Stewart et al., 2005
   Obese Zucker Lean p.o. for 15 d 10 1 mM 89 110 100* –9 48 Banday et al., 2005
   Five-sixths nephrectomy (infarction) Sham IP for 10 d 10 1.5 (mmol · kg)/d for 10 d 118 145 122* –8 85 Hasdan et al., 2002
   Five-sixths nephrectomy Sham p.o. for 1 wk 6 1 mM 120 180 150* –17 50 Vaziri et al., 2003a
   Five-sixths nephrectomy Sham IP for 10 d 10 1.5 (mmol · kg)/d 118 145 122* –16 85 Hasdan et al., 2002
   Ren-2 transgenic rat SD p.o. for 3 wk 6 1 mM 115 197 194 (N.S.) –2 3 Whaley-Connell et al., 2007
   SD + HS + BSO (30 mM for 12 d) HS p.o. for 12 d 8 1 mM 112 142 114* –20 93 Banday et al., 2007d
   SHR WKY p.o. or s.c. for 2 wk 6–8 2 mM 200 (nmol · kg)/min by minipump 104 p.o., 147 p.o., 128* p.o., 13* p.o., 45 Welch et al., 2005b
104 s.c., 150 s.c., 126* s.c., –16* s.c., 52
   SHR WKY p.o. from wk 6–11 6 1 mM 143 171 137* –20* 105 Nabha et al., 2005
   SHR SD p.o. for 5 - 15 d 10 1 mM 5 d, 118 5 d, 149 5 d, 143 (N.S.) 5 d, –4 20 de Richelieu et al., 2005
15 d, 124 15 d, 179 15 d, 165 (N.S.) 15 d, –8 25
   SHR WKY p.o. from 0–15 wk 6–12 170 (μmol · kg)/d 100 181 156* –14 30 Fortepiani and Reckelhoff, 2005
   SHR WKY p.o. from 9–15 wk 6–12 170 (μmol · kg)/d 100 195 163* –16 34 Fortepiani and Reckelhoff, 2005
   SHR Untreated SHR p.o. for 4 d at 13–14 wk 10 1 mM 108 (WKY) 199 177* –11 24 Feng et al., 2001
   SHR Untreated SHR p.o. for 7 wk from 5–12 wk 7 1 mM 108 (WKY) 187 167* –11 25 Feng et al., 2001
   SHR WKY p.o. for 2 wk 8 1 mM 118 162 134* –17 63 Schnackenberg and Wilcox, 1999
   SHR WKY i.p. for 7 d 7 1.5 (mmol · kg)/d 97 133 120* –10 36 Schnackenberg et al., 1998
   SHR aging (16 mo) Untreated SHR p.o. for 8 mo from 8–16 mo 6 6 mM 108 185 160* –14 34 Fortepiani et al., 2003
   SHR aging (16 mo) Untreated SHR p.o. for 8 mo 10 1 mM 108 188 161* –14 33 Payne et al., 2003
   SHR aging female (16 mo) Untreated SHR female p.o. for 8 mo from 8–16 mo 6 6 mM 108 195 195 (N.S.) 0 0 Fortepiani et al., 2003
   SHR female WKY p.o. from 0–15 wk 6–12 170 (μmol · kg)/d 101 172 127* –26 63 Fortepiani and Reckelhoff, 2005
   SHR female WKY p.o. from 9–15 wk 6–12 170 (μmol · kg)/d 101 160 159 (N.S.) –1 1 Fortepiani and Reckelhoff, 2005
   SHRSP, Mg2+-deficient Untreated SHRSP p.o. for 7 wk 6 1 mM 108 240 195* –19 30 Touyz et al., 2002
   SHRSP, 4% salt Untreated SHRSP p.o. for 6 wk 6 1 mM 108 260 220* –15 25 Park et al., 2002
   UNX, aldosterone (0.75 μg/h), s.c. salt 8% for 6 wk Vehicle p.o. for 4 wk 27 6 mM 139 236 131* –45 100 Shibata et al., 2007
   UNX, aldosterone (75 pg/h), 1% NaCl for 3 wk Vehicle p.o. for 3 wk ? 2 mM 118 186 158* –8 41 Hirono et al., 2007
Studies in hypertensive rats with intracerebroventricular tempol
   SHR Untreated SHR i.c.v. for 2 wk 6 13.2 μmol/d 163 209 210 (N.S.) 0 0 Kagiyama et al., 2000
Studies in hypertensive mice with systemic tempol
   Ang II (0.7 (mg · kg)/d), WT mice Vehicle s.c. for 2 wk 6 28 (mmol · kg)/d 95 154 128* –17 44 Dikalova et al., 2005
   Ang II (0.7 (mg · kg)/d), Nox-1-overexpressing mice Vehicle s.c. for 2 wk 6 28 (mmol · kg)/d 95 175 138* –21 46 Dikalova et al., 2005
   ET-B-deficient; 8% NaCl WT; 8% NaCl p.o. for 1 wk 20 1 mM 134 183 143* –22 82 Sullivan et al., 2006
   ET-B-deficient; 8% NaCl WT; 8% NaCl p.o. for 2 wk 20 1 mM 134 174 158* –9 40 Sullivan et al., 2006
  • HS, high salt; LS, low salt; DSR, Dahl salt-resistant rat; UNX, uninephrectomized; Dex, dexamethasone; NS, normal salt; HTN, hypertension; ?, unknown; i.c.v., intracerebroventricular; WT, wild type; ACTH, adrenocorticotropin; d, day(s); wk, week(s); mo, month(s)

  • * Significant change with tempol

  • Value is for MAP