doi: 10.1161/hq0102.101127
© 2002 American Heart Association, Inc.
Vascular Biology |
Xanthine Oxidase–Derived Reactive Oxygen Species Convert Flow-Induced Arteriolar Dilation to Constriction in Hyperhomocysteinemia
Possible Role of Peroxynitrite
From the Department of Pathophysiology, Semmelweis University, H-1445, Budapest, Hungary, and the Department of Physiology, New York Medical College, Valhalla, NY.
Correspondence to Akos Koller, MD, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail koller{at}nymc.edu
We hypothesized that in hyperhomocysteinemia (HHcy), flow-induced arteriolar constriction is due to an enhanced generation of reactive oxygen and/or nitrogen species, causing an impairment of nitric oxide (NO) and prostaglandin mediation of the response. Changes in diameter of isolated, pressurized (at 80 mm Hg) gracilis muscle arterioles (diameter 
170 µm) from control and methionine diet–induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 µL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30±4 µm) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32±3 µm), which were abolished by the thromboxane A2 receptor blocker SQ 29,548. Intraluminal administration of superoxide dismutase plus catalase did not affect flow-mediated dilations of control arterioles, but in HHcy arterioles, it reversed the flow-induced constrictions to dilations (maximum 18±4 µm), which were abolished by an NO synthase inhibitor. Flow-induced constrictions of HHcy arterioles were prevented by the presence of the xanthine oxidase inhibitor oxypurinol [but not by the NAD(P)H-oxidase inhibitor diphenyleneiodonium] and by urate, a known peroxynitrite scavenger. Also, authentic peroxynitrite elicited arteriolar constrictions (-31±8 µm) that were eliminated by urate and SQ 29,548. Thus, we suggest that in HHcy, xanthine oxidase–derived superoxide scavenges NO released to flow, forming peroxynitrite, which promotes release of thromboxane A2, resulting in arteriolar constriction.
Key Words: homocysteine • arterioles • flow-induced constriction • thromboxane A2 • reactive oxygen species • xanthine oxidase
This article has been cited by other articles:
 |
|
 |
|
  P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Erdei, A. Toth, E. T. Pasztor, Z. Papp, I. Edes, A. Koller, and Z. Bagi High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: role of xanthine oxidase-derived superoxide anion Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2107 - H2115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koller and Z. Bagi Nitric oxide and H2O2 contribute to reactive dilation of isolated coronary arterioles Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2461 - H2467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cseko, Z. Bagi, and A. Koller Biphasic effect of hydrogen peroxide on skeletal muscle arteriolar tone via activation of endothelial and smooth muscle signaling pathways J Appl Physiol, September 1, 2004; 97(3): 1130 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Bagi, C. Cseko, E. Toth, and A. Koller Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2277 - H2283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kogler, H. Fraser, S. McCune, R. Altschuld, and E. Marban Disproportionate enhancement of myocardial contractility by the xanthine oxidase inhibitor oxypurinol in failing rat myocardium Cardiovasc Res, September 1, 2003; 59(3): 582 - 592. [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]
|
|
|
|
 |
|
 P. A. Fischer, G. N. Dominguez, L. A. Cuniberti, V. Martinez, J. P. Werba, A. J. Ramirez, and L. D. Masnatta Hyperhomocysteinemia Induces Renal Hemodynamic Dysfunction: Is Nitric Oxide Involved? J. Am. Soc. Nephrol., March 1, 2003; 14(3): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ungvari, A. Csiszar, J. G. Edwards, P. M. Kaminski, M. S. Wolin, G. Kaley, and A. Koller Increased Superoxide Production in Coronary Arteries in Hyperhomocysteinemia: Role of Tumor Necrosis Factor-{alpha}, NAD(P)H Oxidase, and Inducible Nitric Oxide Synthase Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 418 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Sohn, F. Krotz, S. Zahler, T. Gloe, M. Keller, K. Theisen, T. M Schiele, V. Klauss, and U. Pohl Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation Cardiovasc Res, March 1, 2003; 57(3): 804 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guthikonda, C. Sinkey, T. Barenz, and W. G. Haynes Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers Circulation, January 28, 2003; 107(3): 416 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dayal, K. L. Brown, C. J. Weydert, L. W. Oberley, E. Arning, T. Bottiglieri, F. M. Faraci, and S. R. Lentz Deficiency of Glutathione Peroxidase-1 Sensitizes Hyperhomocysteinemic Mice to Endothelial Dysfunction Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1996 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Fulton and J. N. Stallone Sexual dimorphism in prostanoid-potentiated vascular contraction: roles of endothelium and ovarian steroids Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2062 - H2073. [Abstract] [Full Text] [PDF]
|
|