Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease. (March 2016)

• Record Type: Journal Article
• Authors: Walker, Meegan A.; Hoier, Birgitte; Walker, Philip J.; Schulze, Karl; Bangsbo, Jens; Hellsten, Ylva; Askew, Christopher D.
• Is Part Of: Atherosclerosis. Volume 246(2016)
• Page Start: 98
• Page End: 105
• Publication Date: 2016-03
• Subjects: Peripheral arterial disease -- Leg blood flow -- Vasoactive enzymes -- NADPH oxidase; AUC area under the curve -- COX cyclooxygenase -- eNOS endothelial nitric oxide synthase -- GAPDH glyceraldehyde 3-phosphase dehydrogenase -- NADPH nicotinamide adenine dinucleotide phosphate -- NO nitric oxide -- PAD peripheral arterial disease -- ROS reactive oxygen species; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.12.029
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: Passive movement hyperaemia was low in PAD suggesting low nitric oxide availability. Leg blood flow during exercise correlated with leg muscle prostacyclin synthase. NADPH oxidase is elevated and leg blood flow is reduced in PAD compared to control.