on February 27, 2006
Published online before print February 27, 2006, doi: 10.1161/01.HYP.0000203161.02046.8d
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 2, 2005
From the Department of Physiology, Medical College of Wisconsin, Milwaukee. * To whom correspondence should be addressed. E-mail: ntaylor{at}mcw.edu.
Abstract--Dahl salt-sensitive (SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt-sensitivity compared with consomic, salt-resistant SS-13BN rats, despite highly similar genetic backgrounds. The present study examined potential sources of renal medullary superoxide in prehypertensive SS rats fed a 0.4% NaCl diet by assessing activity and protein levels of superoxide producing and scavenging enzymes. Superoxide production was nearly doubled in SS rats compared with SS-13BN rats as determined by urinary 8-isoprostane excretion and renal medullary oxy-ethidium microdialysate levels. Medullary superoxide production in tissue homogenates was greater in SS rats, and the NADPH oxidase inhibitor diphenylene iodonium preferentially reduced SS levels to those found in SS-13BN rats. Dinitrophenol, a mitochondrial uncoupler, eliminated the remaining superoxide production in both strains, whereas inhibition of xanthine oxidase, NO synthase, and cycloxygenase had no effect. L-arginine, NO synthase, superoxide dismutase, catalase, and glutathione peroxidase activities between SS and SS-13BN rats did not differ. Chronic blood pressure responses to a 4% NaCl diet were then determined in the presence or absence of the NADPH oxidase inhibitor apocynin (3.5 µg/kg per minute), chronically delivered directly into the renal medulla. Apocynin infusion reduced renal medullary interstitial superoxide from 1059±130 to 422±80 (oxyethidium fluorescence units) and mean arterial pressure from 175±4 to 157±6 mm Hg in SS rats, whereas no effects on either were observed in the SS-13BN. We conclude that excess renal medullary superoxide production in SS rats contributes to salt-induced hypertension, and NADPH oxidase is the major source of the excess superoxide.
Revised on November 21, 2005
NADPH Oxidase in the Renal Medulla Causes Oxidative Stress and Contributes to Salt-Sensitive Hypertension in Dahl S Rats
Norman E. Taylor*;
Key words: oxidative stress • hypertension, renal • renal disease • sodium • antioxidants
This article has been cited by other articles:
 |
|
 |
|
  Z. Tian, Y. Liu, K. Usa, D. Mladinov, Y. Fang, X. Ding, A. S. Greene, A. W. Cowley Jr, and M. Liang Novel Role of Fumarate Metabolism in Dahl-Salt Sensitive Hypertension Hypertension, August 1, 2009; 54(2): 255 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. O'Connor, L. Lu, M. Liang, and A. W. Cowley Jr A Novel Amiloride-Sensitive H+ Transport Pathway Mediates Enhanced Superoxide Production in Thick Ascending Limb of Salt-Sensitive Rats, Not Na+/H+ Exchange Hypertension, August 1, 2009; 54(2): 248 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jin, C. Hu, A. Polichnowski, T. Mori, M. Skelton, S. Ito, and A. W. Cowley Jr Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production Hypertension, June 1, 2009; 53(6): 1048 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, D. Mladinov, J. L. Pietrusz, K. Usa, and M. Liang Glucocorticoid response elements and 11{beta}-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression Cardiovasc Res, January 1, 2009; 81(1): 140 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, R. J. Singh, K. Usa, B. C. Netzel, and M. Liang Renal medullary 11{beta}-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension Physiol Genomics, December 12, 2008; 36(1): 52 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tian, R. S. Moore, W. E. Phillips, L. Lin, S. Braddy, J. S. Pryor, R. L. Stockstill, M. D. Hughson, and R. D. Manning Jr. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1858 - R1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cowley Jr Renal Medullary Oxidative Stress, Pressure-Natriuresis, and Hypertension Hypertension, November 1, 2008; 52(5): 777 - 786. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kelsen, B. J. Patel, L. B. Parker, T. Vera, J. M. Rimoldi, R. S. V. Gadepalli, H. A. Drummond, and D. E. Stec Heme oxygenase attenuates angiotensin II-mediated superoxide production in cultured mouse thick ascending loop of Henle cells Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1158 - F1165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vera, S. Kelsen, and D. E. Stec Kidney-Specific Induction of Heme Oxygenase-1 Prevents Angiotensin II Hypertension Hypertension, October 1, 2008; 52(4): 660 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. O'Connor, L. Lu, C. Schreck, and A. W. Cowley Jr. Enhanced amiloride-sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats Am J Physiol Renal Physiol, September 1, 2008; 295(3): F726 - F733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mori, A. Polichnowski, P. Glocka, M. Kaldunski, Y. Ohsaki, M. Liang, and A. W. Cowley Jr. High Perfusion Pressure Accelerates Renal Injury in Salt-Sensitive Hypertension J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1472 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lopez-Ruiz, J. Sartori-Valinotti, L. L. Yanes, R. Iliescu, and J. F. Reckelhoff Sex differences in control of blood pressure: role of oxidative stress in hypertension in females Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H466 - H474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liang, N. H. Lee, H. Wang, A. S. Greene, A. E. Kwitek, M. L. Kaldunski, T. V. Luu, B. C. Frank, S. Bugenhagen, H. J. Jacob, et al. Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats Physiol Genomics, June 1, 2008; 34(1): 54 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Shen, M. Hagiwara, Y.-Y. Yao, L. Chao, and J. Chao Salutary Effect of Kallistatin in Salt-Induced Renal Injury, Inflammation, and Fibrosis via Antioxidative Stress Hypertension, May 1, 2008; 51(5): 1358 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Tian, A. S. Greene, K. Usa, I. R. Matus, J. Bauwens, J. L. Pietrusz, A. W. Cowley Jr, and M. Liang Renal Regional Proteomes in Young Dahl Salt-Sensitive Rats Hypertension, April 1, 2008; 51(4): 899 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Tian, A. S. Greene, J. L. Pietrusz, I. R. Matus, and M. Liang MicroRNA-target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis Genome Res., March 1, 2008; 18(3): 404 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fujita, K. Ando, A. Nagae, and T. Fujita Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Salt-Sensitive Hypertension Hypertension, August 1, 2007; 50(2): 360 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Usa, R. J. Singh, B. C. Netzel, Y. Liu, H. Raff, and M. Liang Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F186 - F192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mori, P. M. O'Connor, M. Abe, and A. W. Cowley Jr Enhanced Superoxide Production in Renal Outer Medulla of Dahl Salt-Sensitive Rats Reduces Nitric Oxide Tubular-Vascular Cross-Talk Hypertension, June 1, 2007; 49(6): 1336 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vera, S. Kelsen, L. L. Yanes, J. F. Reckelhoff, and D. E. Stec HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1472 - R1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brault, F. Gobeil Jr., A. Fortier, J.-C. Honore, J.-S. Joyal, P. S. Sapieha, A. Kooli, E. Martin, P. Hardy, A. Ribeiro-da-Silva, et al. Lysophosphatidic acid induces endothelial cell death by modulating the redox environment Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1174 - R1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Taylor, K. G. Maier, R. J. Roman, and A. W. Cowley Jr NO Synthase Uncoupling in the Kidney of Dahl S Rats: Role of Dihydrobiopterin Hypertension, December 1, 2006; 48(6): 1066 - 1071. [Abstract] [Full Text] [PDF]
|
|