Published online before print April 13, 2001, doi: 10.1161/hh0801.089341
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© 2001 American Heart Association, Inc.
Integrative Physiology |
Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions
Role of Oxidative Stress
From the Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to Gail D. Thomas, PhD, University of Texas Southwestern Medical Center, Hypertension Division, 5323 Harry Hines Blvd, Dallas, TX 75390-8586. E-mail gail.thomas{at}utsouthwestern.edu
Abstract—Skeletal muscle perfusion during exercise is impaired in heart failure, but the underlying mechanisms are poorly understood. One possibility is that sympathetic vasoconstriction is enhanced in exercising muscle in heart failure as a result of impaired counterregulatory mechanisms that normally act to attenuate vasoconstrictor responses. In healthy animals, sympathetic vasoconstriction in contracting skeletal muscle is attenuated by endogenously produced nitric oxide (NO). Because the NO pathway may be dysfunctional in heart failure, we hypothesized that reduced NO in contracting muscle would result in enhanced sympathetic vasoconstriction. In sham rats and rats with chronic myocardial infarctions (MIs) produced by coronary artery ligation, we measured arterial pressure and femoral artery blood flow responses to sympathetic nerve stimulation (1, 2.5, and 5 Hz) in resting and contracting hindlimb. In resting hindlimb, sympathetic stimulation decreased femoral vascular conductance similarly in sham and MI rats. In contracting hindlimb, these vasoconstrictor responses were attenuated to a greater extent in sham than in MI rats. NO synthase inhibition enhanced sympathetic vasoconstriction in contracting hindlimb of sham, but not MI, rats. Conversely, infusion of L-arginine or a superoxide scavenger, tempol or tiron, attenuated sympathetic vasoconstriction in contracting hindlimb of MI rats. NO synthase expression was similar, but malondialdehyde (a marker of free radical damage) was greater in skeletal muscle from MI than from sham rats. These data suggest that impaired metabolic modulation of sympathetic vasoconstriction in contracting skeletal muscle of MI rats is a consequence of superoxide-mediated disruption of the NO pathway.
Key Words: vasoconstriction • oxidant stress • nitric oxide • skeletal muscle • heart failure
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