| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: azou{at}mcw.edu.
A membrane-permeable superoxide dismutase (SOD) mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL) has been used as an antioxidant to prevent hypertension. However, we recently found that this SOD mimetic could not prevent the development of hypertension induced by inhibition of renal medullary SOD with diethyldithiocarbamic acid (DETC), unless catalase was co-administrated in the renal medulla. Since TEMPOL dismutes superoxide (O2.-) to produce H2O2, it is possible that increased H2O2 counteracts the effects of TEMPOL on renal medullary blood flow (MBF) and sodium excretion (UNaV), thereby restraining the antihypertensive effect of this SOD mimetic during exaggerated oxidative stress in the kidney. The present study was designed to test this hypothesis. By in vivo microdialysis and AmplexTM Red H2O2 microassay, it was found that interstitial H2O2 levels in the renal cortex and medulla in anesthetized rats averaged 55.91 ± 3.66 and 102.18 ± 5.16 nM, respectively. Renal medullary interstitial infusion (R.I.) of TEMPOL (30 µmol/min/kg) significantly increased medullary H2O2 levels by 46%, which was completely abolished by co-infusion of catalase (10 mg/min/kg). Functionally, the removal of H2O2 by catalase enhanced TEMPOL-induced increase in MBF, urine flow (UV) and UNaV by 28%, 41% and 30%, respectively. This suggests that H2O2 may produce renal medullary vasoconstriction and decrease water and sodium excretion. Indeed, direct delivery of H2O2 (7.5-30 nmol/min/kg, R.I.) into the renal medulla significantly decreased renal MBF, UV and UNaV, and catalase reversed the effects of H2O2. We conclude that TEMPOL produces renal medullary vasodilator effect and results in diuresis and natriuresis. However, this SOD mimetic increases the formation of H2O2, which constricts medullary vessels and thereby counteracts its vasodilator actions. This counteracting effect of H2O2 may plague the use of TEMPOL as an antihypertensive agent under exaggerated oxidative stress in the kidney.
This article has been cited by other articles:
|
|
 |
|
  C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Just, C. L. Whitten, and W. J. Arendshorst Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors Am J Physiol Renal Physiol, April 1, 2008; 294(4): F719 - F728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liberman, E. Bassi, M. K. Martinatti, F. C. Lario, J. Wosniak Jr, P. M.A. Pomerantzeff, and F. R.M. Laurindo Oxidant Generation Predominates Around Calcifying Foci and Enhances Progression of Aortic Valve Calcification Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, A. Pearlman, Z. Luo, and C. S. Wilcox Hydrogen peroxide mediates a transient vasorelaxation with tempol during oxidative stress Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2085 - H2092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Edwards, W. A. Macdonald, C. van der Poel, and D. G. Stephenson O2bullet production at 37{degrees}C plays a critical role in depressing tetanic force of isolated rat and mouse skeletal muscle Am J Physiol Cell Physiol, August 1, 2007; 293(2): C650 - C660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Sullivan, J. M. Sasser, and J. S. Pollock Sexual dimorphism in oxidant status in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R764 - R768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Just, A. J. M. Olson, C. L. Whitten, and W. J. Arendshorst Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H83 - H92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abe, P. O'Connor, M. Kaldunski, M. Liang, R. J. Roman, and A. W. Cowley Jr. Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb Am J Physiol Renal Physiol, August 1, 2006; 291(2): F350 - F357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xia, H. Wang, H. J. Goldberg, S. Munk, I. G. Fantus, and C. I. Whiteside Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression Am J Physiol Renal Physiol, February 1, 2006; 290(2): F345 - F356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Juncos, N. J. Hong, and J. L. Garvin Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in the thick ascending limb Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R79 - R83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan, A. Castillo, L. G. Navar, and D. S. A. Majid Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats Am J Physiol Renal Physiol, January 1, 2006; 290(1): F80 - F86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Taylor and A. W. Cowley Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1573 - R1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Fellner and W. J. Arendshorst Angiotensin II, reactive oxygen species, and Ca2+ signaling in afferent arterioles Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1012 - F1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Li, G. Zhang, F.-X. Yi, A.-P. Zou, and P.-L. Li Activation of NAD(P)H oxidase by outward movements of H+ ions in renal medullary thick ascending limb of Henle Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1048 - F1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, X. Bian, S. W. Watts, and A. Hlavacova Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats Hypertension, November 1, 2005; 46(5): 1154 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan and D. S. A. Majid Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency Hypertension, October 1, 2005; 46(4): 1026 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. A. Majid, A. Nishiyama, K. E. Jackson, and A. Castillo Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs Am J Physiol Renal Physiol, February 1, 2005; 288(2): F412 - F419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, K. Rhinehart, G. Solis, J. Pittner, W. Lee-Kwon, W. J. Welch, C. S. Wilcox, and T. L. Pallone Chronic ANG II infusion increases NO generation by rat descending vasa recta Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H29 - H36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. A. Majid, A. Nishiyama, K. E. Jackson, and A. Castillo Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R27 - R32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mori and A. W. Cowley Jr. Role of Pressure in Angiotensin II-Induced Renal Injury: Chronic Servo-Control of Renal Perfusion Pressure in Rats Hypertension, April 1, 2004; 43(4): 752 - 759. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
