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

• Published in: Atherosclerosis Vol. 246; pp. 98 - 105
• Main Authors: Walker, Meegan A, Hoier, Birgitte, Walker, Philip J, Schulze, Karl, Bangsbo, Jens, Hellsten, Ylva, Askew, Christopher D
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2016
• Subjects: Aged; Ankle Brachial Index; Blood Flow Velocity; Cardiovascular; Case-Control Studies; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cytochrome P-450 Enzyme System - metabolism; Exercise; Female; Femoral Artery - physiopathology; Humans; Hyperemia - physiopathology; Intramolecular Oxidoreductases - metabolism; Leg blood flow; Male; Middle Aged; NADPH oxidase; NADPH Oxidases - metabolism; Nitric Oxide Synthase Type III - metabolism; Peripheral arterial disease; Peripheral Arterial Disease - diagnosis; Peripheral Arterial Disease - enzymology; Peripheral Arterial Disease - physiopathology; Phosphorylation; Quadriceps Muscle - enzymology; Regional Blood Flow; Thromboxane-A Synthase - metabolism; Time Factors; Ultrasonography, Doppler; Vasoactive enzymes; NADPH; NO; eNOS; nitric oxide; Vasoactive enzymes; Leg blood flow; nicotinamide adenine dinucleotide phosphate; Peripheral arterial disease; cyclooxygenase; area under the curve; glyceraldehyde 3-phosphase dehydrogenase; COX; AUC; PAD; NADPH oxidase; ROS; reactive oxygen species; endothelial nitric oxide synthase; GAPDH
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.12.029

Abstract 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.