Inefficient functional sympatholysis is an overlooked cause of malperfusion in contracting skeletal muscle

• Published in: The Journal of physiology Vol. 590; no. 24; pp. 6269 - 6275
• Main Authors: Saltin, Bengt, Mortensen, Stefan P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2012; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Adenosine Triphosphate - metabolism; Age Factors; Aging; Animals; Biochemistry; Blood Vessels - innervation; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - physiopathology; Energy Metabolism; Exercise; Exercise (effects); Female; Hemodynamics; Humans; Legs; Male; Men; Muscle Contraction; Muscle, Skeletal - blood supply; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Muscles (activity); Musculoskeletal system; Nitric Oxide - metabolism; Physical fitness; Physiology; Receptors, Purinergic P2 - metabolism; Regional Blood Flow; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Symposium Section Reviews: Blood Flow Regulation: From Rest to Maximal Exercise; Tyramine - metabolism; Vasoconstriction; Vasodilation; Youth
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/jphysiol.2012.241026

Contracting skeletal muscle can overcome sympathetic vasoconstrictor activity (functional sympatholysis), which allows for a blood supply that matches the metabolic demand. This ability is thought to be mediated by locally released substances that modulate the effect of noradrenaline (NA) on the α‐receptor. Tyramine induces local NA release and can be used in humans to investigate the underlying mechanisms and physiological importance of functional sympatholysis in the muscles of healthy and diseased individuals as well as the impact of the active muscles’ training status. In sedentary elderly men, functional sympatholysis and muscle blood flow are impaired compared to young men, but regular physical activity can prevent these age related impairments. In young subjects, two weeks of leg immobilization causes a reduced ability for functional sympatholysis, whereas the trained leg maintained this function. Patients with essential hypertension have impaired functional sympatholysis in the forearm, and reduced exercise hyperaemia in the leg, but this can be normalized by aerobic exercise training. The effect of physical activity on the local mechanisms that modulate sympathetic vasoconstriction is clear, but it remains uncertain which locally released substance(s) block the effect of NA and how this is accomplished. NO and ATP have been proposed as important inhibitors of NA mediated vasoconstriction and presently an inhibitory effect of ATP on NA signalling via P2 receptors appears most likely.