(Hypertension. 2001;38:655.)
© 2001 American Heart Association, Inc.
Renin-Angiotensin System |
Antioxidants Block Angiotensin II-Induced Increases in Blood Pressure and Endothelin
Department of Physiology and Biophysics (M.C.O., M.C.M., J.C.R., L.A.J.) and Division of Nephrology (L.A.J.), Mayo School of Medicine, Mayo Clinic, Rochester, Minn
Correspondence to Luis A Juncos, Division of Nephrology, Mayo Clinic, Guggenheim Bldg 942A, 200 First St SW, Rochester, MN 55905. E-Mail Juncos.Luis{at}Mayo.Edu
Abstract
Abstract—— Chronically infusing a subpressor dose of angiotensin (Ang) II increases blood pressure via poorly defined mechanisms. We found that this hypertensive response is accompanied by increased oxidant stress and is prevented by blocking endothelin (ET) receptors. Thus, we now tested whether blocking oxidant stress decreases both blood pressure and ET levels. We infused Sprague-Dawley rats (via osmotic pumps) with either vehicle (group 1) or Ang II (5 ng · kg-1 · min-1; groups 2 to 4) for 15 days. Groups 3 and 4 also received either tempol in the drinking water (1 mmol/L) or vitamin E (5000 IU/kg diet), respectively, for 15 days. We measured systolic blood pressure (SBP) and urinary nitrite excretion every 3 days, and on day 15 we measured systemic and renal venous plasma levels of ET, isoprostanes, and thiobarbituric acid reactive substances (TBARS). SBP in Group 1 did not change throughout the study, whereas Ang II increased SBP (from 132±5 to 151±7 mm Hg). In addition, Ang II increased the systemic and renal venous levels of isoprostanes, TBARS, and ET and caused a transient decrease in urinary nitrites (that returned to control levels by day 9). Both tempol and vitamin E prevented Ang II-induced hypertension and either prevented or tended to blunt the increase in systemic and renal isoprostanes, TBARS, and ET. Finally, both antioxidants abolished the transient decrease in urinary nitrites. These results together with our previous study suggest that subpressor-dose Ang II increases oxidant stress (and isoprostanes). This in turn increases ET levels, which participate in the hypertensive response to Ang II.
Key Words: angiotensin II • renal blood flow • free radicals • oxidative stress • hypertension, arterial • kidney • antioxidants
This article has been cited by other articles:
 |
|
 |
|
  T. Vera, J. P. Granger, and D. E. Stec Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates ANG II-dependent hypertension in mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R738 - R743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carlstrom, R. D. Brown, J. Sallstrom, E. Larsson, M. Zilmer, S. Zabihi, U. J. Eriksson, and A. E. G. Persson SOD1 deficiency causes salt sensitivity and aggravates hypertension in hydronephrosis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R82 - R92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 D. J. Chess, W. Xu, R. Khairallah, K. M. O'Shea, W. J. Kop, A. M. Azimzadeh, and W. C. Stanley The antioxidant tempol attenuates pressure overload-induced cardiac hypertrophy and contractile dysfunction in mice fed a high-fructose diet Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2223 - H2230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Rajapakse, C. De Miguel, S. Das, and D. L. Mattson Exogenous L-Arginine Ameliorates Angiotensin II-Induced Hypertension and Renal Damage in Rats Hypertension, December 1, 2008; 52(6): 1084 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Cingolani, M. C. Villa-Abrille, M. Cornelli, A. Nolly, I. L. Ennis, C. Garciarena, A. M. Suburo, V. Torbidoni, M. V. Correa, M. C. Camilionde Hurtado, et al. The Positive Inotropic Effect of Angiotensin II: Role of Endothelin-1 and Reactive Oxygen Species Hypertension, April 1, 2006; 47(4): 727 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsuno, H. Yamada, K. Iwata, D. Jin, M. Katsuyama, M. Matsuki, S. Takai, K. Yamanishi, M. Miyazaki, H. Matsubara, et al. Nox1 Is Involved in Angiotensin II-Mediated Hypertension: A Study in Nox1-Deficient Mice Circulation, October 25, 2005; 112(17): 2677 - 2685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dikalova, R. Clempus, B. Lassegue, G. Cheng, J. McCoy, S. Dikalov, A. S. Martin, A. Lyle, D. S. Weber, D. Weiss, et al. Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice Circulation, October 25, 2005; 112(17): 2668 - 2676. [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]
|
|
|
|
|
|
R. J. Bolterman, M. C. Manriquez, M. C. O. Ruiz, L. A. Juncos, and J. C. Romero Effects of Captopril on the Renin Angiotensin System, Oxidative Stress, and Endothelin in Normal and Hypertensive Rats Hypertension, October 1, 2005; 46(4): 943 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Campese, Y. Shaohua, and Z. Huiquin Oxidative Stress Mediates Angiotensin II-Dependent Stimulation of Sympathetic Nerve Activity Hypertension, September 1, 2005; 46(3): 533 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Ullian, A. K. Gelasco, W. R. Fitzgibbon, C. N. Beck, and T. A. Morinelli N-Acetylcysteine Decreases Angiotensin II Receptor Binding in Vascular Smooth Muscle Cells J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2346 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sharma, A. Cook, M. Smith, C. Valancius, and E. W. Inscho TGF-{beta} impairs renal autoregulation via generation of ROS Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1069 - F1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Shah Role of the renin-angiotensin system in the pathogenesis of preeclampsia Am J Physiol Renal Physiol, April 1, 2005; 288(4): F614 - F625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Pollock Endothelin, Angiotensin, and Oxidative Stress in Hypertension Hypertension, April 1, 2005; 45(4): 477 - 480. [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]
|
|
|
|
|
|
W. J. Welch, J. Blau, H. Xie, T. Chabrashvili, and C. S. Wilcox Angiotensin-induced defects in renal oxygenation: role of oxidative stress Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H22 - H28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. del Villar, C. J. G. Alonso, C. A. Feldstein, L. A. Juncos, and J. C. Romero Role of Endothelin in the Pathogenesis of Hypertension Mayo Clin. Proc., January 1, 2005; 80(1): 84 - 96. [Abstract] [PDF]
|
|
|
|
|
|
N. Lu, B. G. Helwig, R. J. Fels, S. Parimi, and M. J. Kenney Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2626 - H2633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Varela, M. Herrera, and J. L. Garvin Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2- and is diminished by a high-salt diet Am J Physiol Renal Physiol, August 1, 2004; 287(2): F224 - F230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Zimmerman, E. Lazartigues, R. V. Sharma, and R. L. Davisson Hypertension Caused by Angiotensin II Infusion Involves Increased Superoxide Production in the Central Nervous System Circ. Res., July 23, 2004; 95(2): 210 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, T. Chabrashvili, and C. S. Wilcox Enhanced Contractility of Renal Afferent Arterioles From Angiotensin-Infused Rabbits: Roles of Oxidative Stress, Thromboxane Prostanoid Receptors, and Endothelium Circ. Res., June 11, 2004; 94(11): 1436 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Chade, J. D. Krier, M. Rodriguez-Porcel, J. F. Breen, M. A. McKusick, A. Lerman, and L. O. Lerman Comparison of acute and chronic antioxidant interventions in experimental renovascular disease Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1079 - F1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Parkington, J. Dodd, S. E. Luff, K. Worthy, H. A. Coleman, M. Tare, W. P. Anderson, and A. J. Edgley Selective Increase in Renal Arcuate Innervation Density and Neurogenic Constriction in Chronic Angiotensin II-Infused Rats Hypertension, March 1, 2004; 43(3): 643 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 H.-J. Hong, P. Chan, J.-C. Liu, S.-H. Juan, M.-T. Huang, J.-G. Lin, and T.-H. Cheng Angiotensin II induces endothelin-1 gene expression via extracellular signal-regulated kinase pathway in rat aortic smooth muscle cells Cardiovasc Res, January 1, 2004; 61(1): 159 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Brands, T. D. Bell, and B. Gibson Nitric Oxide May Prevent Hypertension Early in Diabetes by Counteracting Renal Actions of Superoxide Hypertension, January 1, 2004; 43(1): 57 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Zhang, S. Kimura, A. Nishiyama, T. Shokoji, M. Rahman, and Y. Abe ROS During the Acute Phase of Ang II Hypertension Participates in Cardiovascular MAPK Activation But Not Vasoconstriction Hypertension, January 1, 2004; 43(1): 117 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rodrigo, W. Passalacqua, J. Araya, M. Orellana, and G. Rivera Homocysteine and Essential Hypertension J. Clin. Pharmacol., December 1, 2003; 43(12): 1299 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lopez, M. G. Salom, B. Arregui, F. Valero, and F. J. Fenoy Role of Superoxide in Modulating the Renal Effects of Angiotensin II Hypertension, December 1, 2003; 42(6): 1150 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Cheng, P.-Y. Cheng, N.-L. Shih, I.-B. Chen, D. L. Wang, and J.-J. Chen Involvement of reactive oxygen species in angiotensin II-induced endothelin-1 gene expression in rat cardiac fibroblasts J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1845 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, Y. Chen, T. Chabrashvili, S. Aslam, L. J. Borrego Conde, J. G. Umans, and C. S. Wilcox Role of Oxidative Stress in Endothelial Dysfunction and Enhanced Responses to Angiotensin II of Afferent Arterioles from Rabbits Infused with Angiotensin II J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2783 - 2789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rugale, S. Delbosc, J.-P. Cristol, A. Mimran, and B. Jover Sodium restriction prevents cardiac hypertrophy and oxidative stress in angiotensin II hypertension Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1744 - H1750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
N. J. Schork, J. P. Gardner, L. Zhang, D. Fallin, B. Thiel, H. Jakubowski, and A. Aviv Genomic Association/Linkage of Sodium Lithium Countertransport in CEPH Pedigrees Hypertension, November 1, 2002; 40(5): 619 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Delbosc, J.-P. Cristol, B. Descomps, A. Mimran, and B. Jover Simvastatin Prevents Angiotensin II-Induced Cardiac Alteration and Oxidative Stress Hypertension, August 1, 2002; 40(2): 142 - 147. [Abstract] [Full Text] [PDF]
|
|