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(Hypertension. 1999;33:424-428.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F2
From the Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC.
Correspondence to Christine G. Schnackenberg, PhD, Georgetown University Medical Center, Division of Nephrology and Hypertension, Bldg D, Room 385, 4000 Reservoir Rd NW, Washington, DC 20007.
Abstract—8-Iso
prostaglandin F2
(8-ISO) is formed
nonenzymatically from the attack of superoxide radical on
arachidonic acid. Therefore, 8-ISO is a marker of
oxidative stress in vivo. We have recently shown that short-term
administration of the membrane-permeable, metal-independent superoxide
dismutase mimetic tempol (4-hydroxy-2, 2, 6, 6-tetramethyl
piperidinoxyl) normalizes blood pressure in spontaneously
hypertensive rats (SHR). The present study was designed to test
whether prolonged administration of tempol ameliorates oxidative stress
and hypertension in SHR. In control SHR (n=8), mean
arterial pressure and heart rate were increased and renal
blood flow and glomerular filtration rate were reduced
compared with control Wistar-Kyoto rats (WKY) (n=7). Twenty-four-hour
renal excretion of 8-ISO was significantly increased in SHR compared
with WKY. Two weeks of tempol administration in the drinking water
(1 mmol/L) to SHR (n=8) decreased mean arterial
pressure by 18% (162±8 to 134±6 mm Hg,
P<0.05), increased glomerular filtration
rate by 17% (1.6±0.2 to 1.9±0.3 mL/min), and decreased renal
excretion of 8-ISO by 39% (9.8±0.7 to 6.0±0.7 ng/24 hours,
P<0.05). In contrast, tempol administration to WKY
(n=6) had no significant effect on mean arterial pressure
(115±5 versus 118±8 mm Hg), glomerular filtration
rate (3.0±0.4 versus 2.5±0.5 mL/min), or renal excretion of 8-ISO
(7.9±0.4 versus 6.8±0.7 ng/24 hours). In conclusion, the SHR is a
model of hypertension and renal vasoconstriction associated with
oxidative stress. Because long-term administration of a superoxide
scavenger reduces blood pressure and oxidative stress in vivo, this
study suggests a role for oxygen radicals in the maintenance of
hypertension in SHR.
Key Words: oxidative stress • isoprostanes • oxygen radicals • superoxide dismutase
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 F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]
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M. Asghar and M. F. Lokhandwala Antioxidant Supplementation Normalizes Elevated Protein Kinase C Activity in the Proximal Tubules of Old Rats Experimental Biology and Medicine, March 1, 2004; 229(3): 270 - 275. [Abstract] [Full Text] [PDF]
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A. Nishiyama, M. Yoshizumi, H. Hitomi, S. Kagami, S. Kondo, A. Miyatake, M. Fukunaga, T. Tamaki, H. Kiyomoto, M. Kohno, et al. The SOD Mimetic Tempol Ameliorates Glomerular Injury and Reduces Mitogen-Activated Protein Kinase Activity in Dahl Salt-Sensitive Rats J. Am. Soc. Nephrol., February 1, 2004; 15(2): 306 - 315. [Abstract] [Full Text] [PDF]
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S. H. Mehta, R. C. Webb, A. Ergul, A. Tawak, and A. M. Dorrance Neuroprotection by tempol in a model of iron-induced oxidative stress in acute ischemic stroke Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R283 - R288. [Abstract] [Full Text] [PDF]
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J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]
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H. Xu, G. D. Fink, and J. J. Galligan Tempol Lowers Blood Pressure and Sympathetic Nerve Activity But Not Vascular O2- in DOCA-Salt Rats Hypertension, February 1, 2004; 43(2): 329 - 334. [Abstract] [Full Text] [PDF]
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S. Adler, H. Huang, M. S. Wolin, and P. M. Kaminski Oxidant Stress Leads to Impaired Regulation of Renal Cortical Oxygen Consumption by Nitric Oxide in the Aging Kidney J. Am. Soc. Nephrol., January 1, 2004; 15(1): 52 - 60. [Abstract] [Full Text] [PDF]
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P. Minuz, P. Patrignani, S. Gaino, F. Seta, M. L. Capone, S. Tacconelli, M. Degan, G. Faccini, A. Fornasiero, G. Talamini, et al. Determinants of Platelet Activation in Human Essential Hypertension Hypertension, January 1, 2004; 43(1): 64 - 70. [Abstract] [Full Text] [PDF]
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C. Kitiyakara, T. Chabrashvili, Y. Chen, J. Blau, A. Karber, S. Aslam, W. J. Welch, and C. S. Wilcox Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2775 - 2782. [Abstract] [Full Text] [PDF]
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M. H. Sedeek, M. T. Llinas, H. Drummond, L. Fortepiani, S. R. Abram, B. T. Alexander, J. F. Reckelhoff, and J. P. Granger Role of Reactive Oxygen Species in Endothelin-Induced Hypertension Hypertension, October 1, 2003; 42(4): 806 - 810. [Abstract] [Full Text] [PDF]
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J. A. Payne, J. F. Reckelhoff, and R. A. Khalil Role of oxidative stress in age-related reduction of NO-cGMP-mediated vascular relaxation in SHR Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R542 - R551. [Abstract] [Full Text] [PDF]
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 M. Tepel Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia? Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1439 - 1442. [Full Text] [PDF]
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M. Tepel Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia? Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1439 - 1442. [Full Text]
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T. Chabrashvili, C. Kitiyakara, J. Blau, A. Karber, S. Aslam, W. J. Welch, and C. S. Wilcox Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R117 - R124. [Abstract] [Full Text] [PDF]
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S. Racasan, J. A. Joles, P. Boer, H. A. Koomans, and B. Braam NO dependency of RBF and autoregulation in the spontaneously hypertensive rat Am J Physiol Renal Physiol, July 1, 2003; 285(1): F105 - F112. [Abstract] [Full Text] [PDF]
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S. Meng, G. W. Cason, A. W. Gannon, L. C. Racusen, and R. D. Manning Jr Oxidative Stress in Dahl Salt-Sensitive Hypertension Hypertension, June 1, 2003; 41(6): 1346 - 1352. [Abstract] [Full Text] [PDF]
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J. F. Reckelhoff and J. C. Romero Role of oxidative stress in angiotensin-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R893 - R912. [Abstract] [Full Text] [PDF]
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 Y. Chu, S. Iida, D. D. Lund, R. M. Weiss, G. F. DiBona, Y. Watanabe, F. M. Faraci, and D. D. Heistad Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain Circ. Res., March 7, 2003; 92(4): 461 - 468. [Abstract] [Full Text] [PDF]
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K. M. Hoagland, K. G. Maier, and R. J. Roman Contributions of 20-HETE to the Antihypertensive Effects of Tempol in Dahl Salt-Sensitive Rats Hypertension, March 1, 2003; 41(3): 697 - 702. [Abstract] [Full Text] [PDF]
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C. Zhang, T. W. Hein, W. Wang, and L. Kuo Divergent Roles of Angiotensin II AT1 and AT2 Receptors in Modulating Coronary Microvascular Function Circ. Res., February 21, 2003; 92(3): 322 - 329. [Abstract] [Full Text] [PDF]
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T. Shokoji, A. Nishiyama, Y. Fujisawa, H. Hitomi, H. Kiyomoto, N. Takahashi, S. Kimura, M. Kohno, and Y. Abe Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 266 - 273. [Abstract] [Full Text] [PDF]
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B. Rodriguez-Iturbe, C.-D. Zhan, Y. Quiroz, R. K. Sindhu, and N. D. Vaziri Antioxidant-Rich Diet Relieves Hypertension and Reduces Renal Immune Infiltration in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 341 - 346. [Abstract] [Full Text] [PDF]
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N. Kawada, E. Imai, A. Karber, W. J. Welch, and C. S. Wilcox A Mouse Model of Angiotensin II Slow Pressor Response: Role of Oxidative Stress J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2860 - 2868. [Abstract] [Full Text] [PDF]
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T. Ogihara, T. Asano, K. Ando, Y. Chiba, H. Sakoda, M. Anai, N. Shojima, H. Ono, Y. Onishi, M. Fujishiro, et al. Angiotensin II-Induced Insulin Resistance Is Associated With Enhanced Insulin Signaling Hypertension, December 1, 2002; 40(6): 872 - 879. [Abstract] [Full Text] [PDF]
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 Y. Sun, J. Zhang, L. Lu, S. S. Chen, M. T. Quinn, and K. T. Weber Aldosterone-Induced Inflammation in the Rat Heart : Role of Oxidative Stress Am. J. Pathol., November 1, 2002; 161(5): 1773 - 1781. [Abstract] [Full Text] [PDF]
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S. Meng, L. J. Roberts II, G. W. Cason, T. S. Curry, and R. D. Manning Jr. Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R732 - R738. [Abstract] [Full Text] [PDF]
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S. Adler and H. Huang Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1788 - 1794. [Abstract] [Full Text] [PDF]
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X. J. Zhou, N. D. Vaziri, X. Q. Wang, F. G. Silva, and Z. Laszik Nitric Oxide Synthase Expression in Hypertension Induced by Inhibition of Glutathione Synthase J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 762 - 767. [Abstract] [Full Text] [PDF]
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C. G. Schnackenberg Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R335 - R342. [Abstract] [Full Text] [PDF]
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T. Chabrashvili, A. Tojo, M. L. Onozato, C. Kitiyakara, M. T. Quinn, T. Fujita, W. J. Welch, and C. S. Wilcox Expression and Cellular Localization of Classic NADPH Oxidase Subunits in the Spontaneously Hypertensive Rat Kidney Hypertension, February 1, 2002; 39(2): 269 - 274. [Abstract] [Full Text] [PDF]
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Y. Ren, O. A. Carretero, and J. L. Garvin Mechanism by Which Superoxide Potentiates Tubuloglomerular Feedback Hypertension, February 1, 2002; 39(2): 624 - 628. [Abstract] [Full Text] [PDF]
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A. Makino, M. M. Skelton, A.-P. Zou, R. J. Roman, and A. W. Cowley Jr Increased Renal Medullary Oxidative Stress Produces Hypertension Hypertension, February 1, 2002; 39(2): 667 - 672. [Abstract] [Full Text] [PDF]
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T. Aizawa, N. Ishizaka, S.-I. Usui, N. Ohashi, M. Ohno, and R. Nagai Angiotensin II and Catecholamines Increase Plasma Levels of 8-Epi-Prostaglandin F2{alpha} With Different Pressor Dependencies in Rats Hypertension, January 1, 2002; 39(1): 149 - 154. [Abstract] [Full Text] [PDF]
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