Reactive Oxygen Species Impair Sympathetic Vasoregulation in Skeletal Muscle in Angiotensin II–Dependent Hypertension
- 1 October 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 48 (4), 637-643
- https://doi.org/10.1161/01.hyp.0000240347.51386.ea
Abstract
Sympathetic vasoconstriction is attenuated in exercising muscle by locally generated vasodilators, including NO. Skeletal muscle also produces reactive oxygen species (ROS), such as superoxide (O 2 − ), which inactivates NO. We, therefore, hypothesized that excessive ROS production would result in enhanced sympathetic vasoconstriction in exercising muscle. To increase O 2 − 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 O 2 − 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.Keywords
This publication has 30 references indexed in Scilit:
- Exercise IntoleranceProgress in Cardiovascular Diseases, 2005
- Characterization of functional urotensin II receptors in human skeletal muscle myoblasts: comparison with angiotensin II receptorsPeptides, 2005
- Combined NO and PG inhibition augments α-adrenergic vasoconstriction in contracting human skeletal muscleAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Role of nitric oxide in exercise sympatholysisJournal of Applied Physiology, 2004
- Reactive Oxygen Species in the VasculatureHypertension, 2003
- Blunted Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Healthy Humans: is Nitric Oxide Obligatory?The Journal of Physiology, 2003
- Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscleThe Journal of Physiology, 2003
- Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulationThe Journal of Physiology, 2003
- Distribution of Angiotensin II Receptor Expression in the Microcirculation of Striated MuscleMicrocirculation, 2001
- Nitric oxide mediates contraction‐induced attenuation of sympathetic vasoconstriction in rat skeletal muscleThe Journal of Physiology, 1998