. Author manuscript; available in PMC: 2009 Dec 1.

Published in final edited form as: Pharmacol Rev. 2008 Dec;60(4):418–469. doi: 10.1124/pr.108.000240

TABLE 3.

Response of indices of oxidative stress to prolonged tempol administration

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/+28-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 $O_{2}^{\bar{\cdot}}$ 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 $O_{2}^{\bar{\cdot}}$ /(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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 nM	8.8	4 d before, 10.4 8 d after, 10	−13/17, d 4/8 (NS/NS)	50/63	Zhang et al., 2004b
DOCA + salt 0.9%	Sham	p.o. for 3 wk	6	1 mM	Aortic $O_{2}^{\bar{\cdot}}$ , 3166 (mU · mg)/min	875	824	−74^*	102	Ghosh et al., 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	$O_{2}^{\bar{\cdot}}$ 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 uninephrec- tomized	p.o. for 2 wk 2 d	6	2 mM	Aortic rings/ $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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^*
SHR_sp low Mg²⁺diet	Untreated SHR_sp	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 $O_{2}^{\bar{\cdot}}$ , 1.2 (nmol ·min)/mg tissue		0.6	−50^*
SHR_sp 4% salt	Untreated SHR_sp	p.o. for 6 wk	6	1 mM	Vascular $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 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 $O_{2}^{\bar{\cdot}}$ , 250 pmol/mg of tissue	75	160	−36^*	51	Dikalova et al., 2005

Mean values are shown.

8-iso, 8-isoprostane PGF₂_α; 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.