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Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients
Author(s) -
Muller Matthew D.,
Drew Rachel C.,
Blaha Cheryl A.,
Mast Jessica L.,
Cui Jian,
Reed Amy B.,
Sinoway Lawrence I.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.241281
Subject(s) - medicine , blood pressure , reflex , supine position , peripheral , claudication , stimulation , anesthesia , mean arterial pressure , angiology , cardiology , arterial disease , heart rate , vascular disease
Key points• Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality. • Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown. • The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation. • In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion.Abstract Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in patients with peripheral arterial disease (PAD). However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Three physiological studies were conducted in patients with PAD and controls. In Protocol 1, subjects underwent 4 min of low‐intensity (0.5–2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, patients with PAD received high‐dose ascorbic acid intravenously before exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was Δ mean arterial pressure (MAP) during the first 20 s of exercise (i.e. the onset of sympathoexcitation by muscle afferents). Compared to controls, patients with PAD had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg with the most affected leg (11 ± 2 vs. 2 ± 1 mmHg) as well as the least affected leg (7 ± 1 vs. 1 ± 1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% with ascorbic acid. Electrically evoked exercise also elicited larger haemodynamic changes in patients with PAD compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle–brachial index, indicating that patients with more severe resting limb ischaemia have a larger BP response to exercise. The BP response to low‐intensity exercise was enhanced in PAD. Chronic limb ischaemia may sensitize muscle afferents and potentiate the BP response to muscle contraction in a dose‐dependent manner.