This Article Full Text Full Text (PDF) All Versions of this Article: 48/4/637    most recent 01.HYP.0000240347.51386.eav1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhao, W. Articles by Thomas, G. D. Search for Related Content PubMed PubMed Citation Articles by Zhao, W. Articles by Thomas, G. D. Related Collections Animal models of human disease Other hypertension Autonomic, reflex, and neurohumoral control of circulation Oxidant stress Related Article

(Hypertension. 2006;48:637.)
© 2006 American Heart Association, Inc.

Original Articles

Reactive Oxygen Species Impair Sympathetic Vasoregulation in Skeletal Muscle in Angiotensin II–Dependent Hypertension

Weiying Zhao; Scott A. Swanson; Jianfeng Ye; Xilong Li; John M. Shelton; Weiguo Zhang; Gail D. Thomas

From the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

Correspondence to Gail D. Thomas, University of Texas Southwestern Medical Center, Hypertension Division, 5323 Harry Hines Blvd, Dallas, TX 75390-8586. E-mail gail.thomas{at}utsouthwestern.edu

Sympathetic vasoconstriction is attenuated in exercising muscle by locally generated vasodilators, including NO. Skeletal muscle also produces reactive oxygen species (ROS), such as superoxide (O₂^–), which inactivates NO. We, therefore, hypothesized that excessive ROS production would result in enhanced sympathetic vasoconstriction in exercising muscle. To increase O₂^– by activating NADPH oxidase, rats underwent chronic infusion of angiotensin II (Ang II) or unilateral renal artery stenosis (2K1C) to increase endogenous Ang II. At rest, sympathetic nerve stimulation (range: 1 to 5 Hz) evoked similar graded decreases in femoral vascular conductance (range, –34% to –66%) in rats infused with vehicle, Ang II, or norepinephrine and in 2K1C or sham-operated rats. These sympathetically mediated decreases in femoral vascular conductance were markedly attenuated during hindlimb contraction in the vehicle, norepinephrine, and sham rats (range, –3% to –26%) and to a lesser degree in the Ang II (range, –16% to –47%) and 2K1C (range, –16% to –45%) rats. In muscles from Ang II and 2K1C rats, ROS were elevated and the NADPH oxidase subunit gp91^phox was upregulated. The O₂^– scavenger tempol restored the normal attenuation of sympathetic vasoconstriction in the contracting hindlimbs of the Ang II and 2K1C rats, but this effect was prevented by pretreatment with an NO synthase inhibitor. Taken together, these data indicate that chronically elevated Ang II increases muscle ROS, which disrupts the normal NO-dependent attenuation of sympathetic vasoconstriction. These findings may have implications for muscle oxidative stress and sympathetic vasoregulation when the renin–angiotensin system is chronically activated.

Key Words: angiotensin • free radicals • sympathetic nervous system • vasoconstriction • muscles

Related Article:

Too Much Is Not Enough: Hypertension and Sympathetic Vasoconstriction in Contracting Muscles

Michael J. Joyner
Hypertension 2006 48: 560-561. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				H.-J. Wang, Y.-X. Pan, W.-Z. Wang, I. H. Zucker, and W. Wang NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex J Appl Physiol, August 1, 2009; 107(2): 450 - 459. [Abstract] [Full Text] [PDF]

				M. J. Joyner Keeping the juices flowing with age: vitamin C and exercise hyperaemia J. Physiol., June 1, 2009; 587(11): 2423 - 2423. [Full Text] [PDF]

				A. V. N. Bacurau, M. A. Jardim, J. C. B. Ferreira, L. R. G. Bechara, C. R. Bueno Jr., T. C. Alba-Loureiro, C. E. Negrao, D. E. Casarini, R. Curi, P. R. Ramires, et al. Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training J Appl Physiol, May 1, 2009; 106(5): 1631 - 1640. [Abstract] [Full Text] [PDF]

				D. W. Wray, S. K. Nishiyama, and R. S. Richardson Role of {alpha}1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H497 - H504. [Abstract] [Full Text] [PDF]

				W. J. Welch Angiotensin II-Dependent Superoxide: Effects on Hypertension and Vascular Dysfunction Hypertension, July 1, 2008; 52(1): 51 - 56. [Full Text] [PDF]

				W. Han, H. Li, V. A. M. Villar, A. M. Pascua, M. I. Dajani, X. Wang, A. Natarajan, M. T. Quinn, R. A. Felder, P. A. Jose, et al. Lipid Rafts Keep NADPH Oxidase in the Inactive State in Human Renal Proximal Tubule Cells Hypertension, February 1, 2008; 51(2): 481 - 487. [Abstract] [Full Text] [PDF]

				A. M. Jonk, A. J. H. M. Houben, R. T. de Jongh, E. H. Serne, N. C. Schaper, and C. D. A. Stehouwer Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension Physiology, August 1, 2007; 22(4): 252 - 260. [Abstract] [Full Text] [PDF]

				S. L. Burke, G. A. Head, G. W. Lambert, and R. G. Evans Renal Sympathetic Neuroeffector Function in Renovascular and Angiotensin II-Dependent Hypertension in Rabbits Hypertension, April 1, 2007; 49(4): 932 - 938. [Abstract] [Full Text] [PDF]

				M. J. Joyner Too Much Is Not Enough: Hypertension and Sympathetic Vasoconstriction in Contracting Muscles Hypertension, October 1, 2006; 48(4): 560 - 561. [Full Text] [PDF]