Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

TY - JOUR

T1 - Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

AU - Walker, Meegan A.

AU - Høier, Birgitte

AU - Walker, Philip J.

AU - Schulze, Karl

AU - Bangsbo, Jens

AU - Hellsten, Ylva

AU - Askew, Christopher D.

N1 - CURIS 2016 NEXS 026

PY - 2016

Y1 - 2016

N2 - Background: Peripheral arterial disease (PAD) is characterised by impaired leg blood flow, which contributes to claudication and reduced exercise capacity. This study investigated to what extent vasoactive enzymes might contribute to altered blood flow in PAD (Fontaine stage II). Methods: We compared femoral artery blood flow during reactive hyperaemia, leg-extension exercise and passive leg movement, and determined the level of vasoactive enzymes in skeletal muscle samples from the vastus lateralis in PAD (n = 10, 68.5 ± 6.5 years) and healthy controls (CON, n = 9, 62.1 ± 12.3 years). Leg blood flow was measured with Doppler ultrasound and muscle protein levels of phosphorylated endothelial nitric oxide synthase, NADPH oxidase, cyclooxygenase 1 and 2, thromboxane synthase, and prostacyclin synthase were determined. Results: Leg blood flow during the initial 90 s of passive leg movement (242 ± 33 vs 441 ± 75 ml min-1, P = 0.03) and during reactive hyperaemia (423 ± 100 vs 1255 ± 175 ml min-1, P = 0.002) was lower in PAD than CON, whereas no significant difference was observed for leg blood flow during exercise (1490 ± 250 vs 1887 ± 349 ml min-1, P = 0.37). PAD had higher NADPH oxidase than CON (1.04 ± 0.19 vs 0.50 ± 0.06 AU, P = 0.02), with no differences for other enzymes. Leg blood flow during exercise was correlated with prostacyclin synthase (P = 0.001). Conclusion: Elevated NADPH oxidase indicates that oxidative stress may be a primary cause of low nitric oxide availability and impaired blood flow in PAD.

AB - Background: Peripheral arterial disease (PAD) is characterised by impaired leg blood flow, which contributes to claudication and reduced exercise capacity. This study investigated to what extent vasoactive enzymes might contribute to altered blood flow in PAD (Fontaine stage II). Methods: We compared femoral artery blood flow during reactive hyperaemia, leg-extension exercise and passive leg movement, and determined the level of vasoactive enzymes in skeletal muscle samples from the vastus lateralis in PAD (n = 10, 68.5 ± 6.5 years) and healthy controls (CON, n = 9, 62.1 ± 12.3 years). Leg blood flow was measured with Doppler ultrasound and muscle protein levels of phosphorylated endothelial nitric oxide synthase, NADPH oxidase, cyclooxygenase 1 and 2, thromboxane synthase, and prostacyclin synthase were determined. Results: Leg blood flow during the initial 90 s of passive leg movement (242 ± 33 vs 441 ± 75 ml min-1, P = 0.03) and during reactive hyperaemia (423 ± 100 vs 1255 ± 175 ml min-1, P = 0.002) was lower in PAD than CON, whereas no significant difference was observed for leg blood flow during exercise (1490 ± 250 vs 1887 ± 349 ml min-1, P = 0.37). PAD had higher NADPH oxidase than CON (1.04 ± 0.19 vs 0.50 ± 0.06 AU, P = 0.02), with no differences for other enzymes. Leg blood flow during exercise was correlated with prostacyclin synthase (P = 0.001). Conclusion: Elevated NADPH oxidase indicates that oxidative stress may be a primary cause of low nitric oxide availability and impaired blood flow in PAD.

KW - Leg blood flow

KW - NADPH oxidase

KW - Peripheral arterial disease

KW - Vasoactive enzymes

U2 - 10.1016/j.atherosclerosis.2015.12.029

DO - 10.1016/j.atherosclerosis.2015.12.029

M3 - Journal article

C2 - 26771386

AN - SCOPUS:84953246862

SN - 0021-9150

VL - 246

SP - 98

EP - 105

JO - Atherosclerosis

JF - Atherosclerosis

ER -