on October 7, 2002
Hypertension. 2002
Published online before print October 7, 2002, doi: 10.1161/01.HYP.0000037063.90643.0B
Published online before print October 7, 2002, doi: 10.1161/01.HYP.0000037063.90643.0B
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 26, 2002
From the BHF Blood Pressure Group, Department of Medicine and Therapeutics (C.A.H., M.J.B., A.F.D.) and the Department of Cardiothoracic Surgery (S.A.-B., G.B.), Western Infirmary, Glasgow, Scotland. * To whom correspondence should be addressed. E-mail: c.a.hamilton{at}clinmed.gla.ac.uk.
Abstract—The NO/superoxide (O2-) balance is a key regulator of endothelial function. O2- levels are elevated in many forms of cardiovascular disease; therefore, decreasing O2- should improve endothelial function. To explore this hypothesis, internal mammary arteries and saphenous veins, obtained from patients undergoing coronary artery revascularization, and aortic and carotid arteries from Wistar-Kyoto and spontaneously hypertensive stroke-prone rats were incubated with O2- dismutase or NAD(P)H oxidase inhibitors. O2- levels were measured using lucigenin chemiluminescence; NO bioavailability was assessed in organ chambers; and mRNA expression of NAD(P)H oxidase components was quantified by use of a Light Cycler. In rat arteries, phenylarsine oxide, 4-(2-aminoethyl)-benzenesulfanyl fluoride, and apocynin all decreased NADH-stimulated O2- production, but only apocynin increased NO bioavailability. In human internal mammary arteries and saphenous veins, apocynin decreased NAD(P)H-stimulated O2- generation and caused vasorelaxation that was endothelium dependent and reversed on addition of the NO synthase inhibitor NG-nitro-L-arginine methyl ester. In addition, it increased NO production from cultured human endothelial saphenous vein cells. Polyethylene-glycolated O2- dismutase also increased NO bioavailability in rat carotid arteries and human blood vessels, but the effects were smaller than those observed with apocynin. NADH-generated O2- and mRNA expression of p22phox, gp91phox, and nox-1 were comparable between the 2 strains of rat. This is the first study to demonstrate pharmacological effects of apocynin in human blood vessels. The increases in NO bioavailability shown here suggest that the NAD(P)H oxidase pathway may be a novel target for drug intervention in cardiovascular disease.
Revised on April 25, 2002
NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels
Carlene A. Hamilton*;
Key words: apocynin • NAD(P)H oxidase • nitric oxide • superoxide • humans • blood vessels
This article has been cited by other articles:
 |
|
 |
|
  X. Zhou, H. G. Bohlen, J. L. Unthank, and S. J. Miller Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2227 - H2233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schluter, U. Zimmermann, C. Protzel, B. Miehe, K.-J. Klebingat, R. Rettig, and O. Grisk Intrarenal artery superoxide is mainly NADPH oxidase-derived and modulates endothelium-dependent dilation in elderly patients Cardiovasc Res, November 12, 2009; (2009) cvp346v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Graham, N. N. Huynh, C. A. Hamilton, E. Beattie, R. A.J. Smith, H. M. Cocheme, M. P. Murphy, and A. F. Dominiczak Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy Hypertension, August 1, 2009; 54(2): 322 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Durrant, D. R. Seals, M. L. Connell, M. J. Russell, B. R. Lawson, B. J. Folian, A. J. Donato, and L. A. Lesniewski Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase J. Physiol., July 1, 2009; 587(13): 3271 - 3285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Larsen, A. H. Bubolz, S. A. Mendoza, K. A. Pritchard Jr, and D. D. Gutterman Bradykinin-Induced Dilation of Human Coronary Arterioles Requires NADPH Oxidase-Derived Reactive Oxygen Species Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 739 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nambiar, S. Viswanathan, B. Zachariah, N. Hanumanthappa, and Sridhar Gopalakrishna Magadi Oxidative Stress in Prehypertension: Rationale for Antioxidant Clinical Trials Angiology, April 1, 2009; 60(2): 221 - 234. [Abstract] [PDF]
|
|
|
|
|
|
S. G. Denniss and J. W. E. Rush Impaired hemodynamics and endothelial vasomotor function via endoperoxide-mediated vasoconstriction in the carotid artery of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1038 - H1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Mayhan, D. M. Arrick, G. M. Sharpe, and H. Sun Nitric oxide synthase-dependent responses of the basilar artery during acute infusion of nicotine Nicotine Tob Res, March 1, 2009; 11(3): 270 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Godbole, X. Lu, X. Guo, and G. S. Kassab NADPH oxidase has a directional response to shear stress Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H152 - H158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schluter, A. C. Steinbach, A. Steffen, R. Rettig, and O. Grisk Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition Cardiovasc Res, November 1, 2008; 80(2): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Heumuller, S. Wind, E. Barbosa-Sicard, H. H.H.W. Schmidt, R. Busse, K. Schroder, and R. P. Brandes Apocynin Is Not an Inhibitor of Vascular NADPH Oxidases but an Antioxidant Hypertension, February 1, 2008; 51(2): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Cong, Z.-L. Xiao, P. Biancani, and J. Behar Reactive oxygen species are messengers in maintenance of human and guinea pig gallbladder tonic contraction Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1244 - G1251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Chan, S. R. Datla, R. Dilley, H. Hickey, G. R. Drummond, and G. J. Dusting Adventitial application of the NADPH oxidase inhibitor apocynin in vivo reduces neointima formation and endothelial dysfunction in rabbits Cardiovasc Res, September 1, 2007; 75(4): 710 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Fu, D. G. Beer, J. Behar, J. Wands, D. Lambeth, and W. Cao cAMP-response Element-binding Protein Mediates Acid-induced NADPH Oxidase NOX5-S Expression in Barrett Esophageal Adenocarcinoma Cells J. Biol. Chem., July 21, 2006; 281(29): 20368 - 20382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Fang, H. Sun, D. M. Arrick, and W. G. Mayhan Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine J Appl Physiol, February 1, 2006; 100(2): 631 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jimenez-Altayo, A. M. Briones, J. Giraldo, A. M. Planas, M. Salaices, and E. Vila Increased Superoxide Anion Production by Interleukin-1{beta} Impairs Nitric Oxide-Mediated Relaxation in Resistance Arteries J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 42 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Al-Benna, C. A. Hamilton, J. D. McClure, P. N. Rogers, G. A. Berg, I. Ford, C. Delles, and A. F. Dominiczak Low-Density Lipoprotein Cholesterol Determines Oxidative Stress and Endothelial Dysfunction in Saphenous Veins From Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 218 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Herman and S. Moncada Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis Eur. Heart J., October 1, 2005; 26(19): 1945 - 1955. [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. T. Mallet Hypoxic modulation of cardiac L-type Ca2+ current: Interaction of reactive oxygen species and {beta}-adrenergic signaling Cardiovasc Res, September 1, 2005; 67(4): 578 - 580. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, J.-C. Mamputu, N. Wiernsperger, and G. Renier Signaling Pathways Involved in Human Vascular Smooth Muscle Cell Proliferation and Matrix Metalloproteinase-2 Expression Induced by Leptin: Inhibitory Effect of Metformin Diabetes, July 1, 2005; 54(7): 2227 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Satoh, S. Fujimoto, Y. Haruna, S. Arakawa, H. Horike, N. Komai, T. Sasaki, K. Tsujioka, H. Makino, and N. Kashihara NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1144 - F1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adler and H. Huang Oxidant stress in kidneys of spontaneously hypertensive rats involves both oxidase overexpression and loss of extracellular superoxide dismutase Am J Physiol Renal Physiol, November 1, 2004; 287(5): F907 - F913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Endemann and E. L. Schiffrin Endothelial Dysfunction J. Am. Soc. Nephrol., August 1, 2004; 15(8): 1983 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Dodd-o, L. E. Welsh, J. D. Salazar, P. L. Walinsky, E. A. Peck, J. G. Shake, D. J. Caparrelli, R. C. Ziegelstein, J. L. Zweier, W. A. Baumgartner, et al. Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H927 - H936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Young and J. W. Funder Eplerenone, But Not Steroid Withdrawal, Reverses Cardiac Fibrosis in Deoxycorticosterone/ Salt-Treated Rats Endocrinology, July 1, 2004; 145(7): 3153 - 3157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kalinowski, I. T. Dobrucki, and T. Malinski Race-Specific Differences in Endothelial Function: Predisposition of African Americans to Vascular Diseases Circulation, June 1, 2004; 109(21): 2511 - 2517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wu, M. H. Noyan Ashraf, M. Facci, R. Wang, P. G. Paterson, A. Ferrie, and B. H. J. Juurlink Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system PNAS, May 4, 2004; 101(18): 7094 - 7099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. I. Anderson, F. Wang, and D. G. Gardner Role of the Epidermal Growth Factor Receptor in Signaling Strain-dependent Activation of the Brain Natriuretic Peptide Gene J. Biol. Chem., March 5, 2004; 279(10): 9287 - 9297. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 Y. Liu, H. Zhao, H. Li, B. Kalyanaraman, A. C. Nicolosi, and D. D. Gutterman Mitochondrial Sources of H2O2 Generation Play a Key Role in Flow-Mediated Dilation in Human Coronary Resistance Arteries Circ. Res., September 19, 2003; 93(6): 573 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adler, E. Messina, B. Sherman, Z. Wang, H. Huang, A. Linke, and T. H. Hintze NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1015 - H1022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Ulker, D. McMaster, P. P. McKeown, and U. Bayraktutan Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation Cardiovasc Res, August 1, 2003; 59(2): 488 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Z. Yang, A. Y. Zhang, F.-X. Yi, P.-L. Li, and A.-P. Zou Redox regulation of HIF-1alpha levels and HO-1 expression in renal medullary interstitial cells Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1207 - F1215. [Abstract] [Full Text] [PDF]
|
|