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Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min -1 ·kg leg mass -1 ), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WL max )], 3) ATP (0.05 µmol·min -1 ·kg leg mass -1 ) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min -1 ·kg leg mass -1 ). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: -3 ± 1 ml·min -1 ·mmHg -1 and controls: -3 ± 1 ml·min -1 ·mmHg -1 , P < 0.05) and 20% WL max (COPD: -4 ± 1 ml·min -1 ·mmHg -1 and controls: -3 ± 1 ml·min -1 ·mmHg -1 , P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: -0.03 ± 0.01 l·min -1 ·kg leg mass -1 vs., Controls: -0.04 ± 0.01 l·min -1 ·kg leg mass -1 , P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained. NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.

Key Points: Rapid onset vasodilatation (ROV) initiates functional hyperaemia upon skeletal muscle contraction and is attenuated during ageing via α-adrenoreceptor (αAR) stimulation, but it is unknown where this effect predominates in resistance networks. In gluteus maximus muscles of young (4 months) and old (24 months) male C57BL/6 mice, tetanic contraction while observing feed arteries and arterioles initiated ROV, which increased with contraction duration, peaked later in upstream versus downstream vessel branches and was attenuated throughout networks with advanced age. With no effect on muscle force production, inhibiting αARs improved ROV in old mice while activating αARs attenuated ROV in young mice. Modulating ROV through αARs was greater in upstream feed arteries and arterioles compared to downstream arterioles, with α 2 ARs more effective than α 1 ARs. ROV is coordinated along resistance networks and modulated differentially between young and old mice via αARs; with advanced age, attenuated dilatation of upstream branches will restrict muscle blood flow., Abstract: Rapid onset vasodilatation (ROV) in skeletal muscle is attenuated during advanced age via α-adrenoreceptor (αAR) activation, but it is unknown where such effects predominate in the resistance vasculature. Studying the gluteus maximus muscle (GM) of anaesthetized young (4 months) and old (24 months) male C57BL/6 mice, we tested the hypothesis that attenuation of ROV during advanced age is most effective in proximal branches of microvascular resistance networks. Diameters of a feed artery (FA) and first- (1A), second- (2A) and third- (3A) order arterioles were studied in response to single tetanic contractions (100 Hz, 100-1000 ms). ROV began within 1 s and peaked sooner in 2A and 3A (∼3 s) than in 1A or FA (∼4 s). Relative amplitudes of dilatation increased with contraction duration and with vessel branch order (FA<1A<2A<3A). In old mice, attenuation of ROV was greater in FA and 1A compared to 2A and 3A. With no effect on muscle force production, inhibiting αARs (phentolamine; 10 -6  m) improved ROV in FA and 1A of old mice while subthreshold stimulation of αARs in young mice (noradrenaline; 10 -9  m) depressed ROV most effectively in FA and 1A. In young mice, stimulating α 1 ARs (phenylephrine; 10 -7  m) and α 2 ARs (UK 14304; 10 -7  m) attenuated ROV primarily in FA. In old mice, inhibiting α 2 ARs (rauwolscine; 10 -7  m) restored ROV more effectively in FA and 1A than did inhibiting α 1 ARs (prazosin; 10 -8  m). We conclude that, with temporal and spatial coordination along resistance networks, attenuation of ROV with advanced age is most effective in proximal branches via constitutive activation of α 2 ARs., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Purpose: The effect of acute activation of the sympathetic nervous system on the dynamic response of muscle hyperaemia during exercise at different intensities is not clear. Methods: To explore this, six men performed 16, 5-min bouts of intermittent calf contractions at two intensities (25 and 50 % MVC) and two levels of sympathetic activation (CPT cold pressor test, CON control). Mean arterial pressure (MAP) and leg vascular conductance (LVC leg blood flow/MAP) were measured during rest and contractions (3 s intervals), and dynamic response characteristics of LVC were estimated using curve-fitting and empirical modeling. Results: MAP was ~20 % greater ( P ≤ 0.05) during CPT than CON before and during initial contractions at both intensities. At 25 % MVC, CPT reduced the exercise-induced change in LVC (0.109 vs 0.125 ml 100 mlminmmHg; P < 0.05), an effect attributed to the reduction in the amplitude of the fast growth phase (0.091 vs 0.128 1 ml 100 mlminmmHg; P < 0.05). At 50 % MVC, CPT also blunted the fast growth phase (0.147 vs 0.189 ml 100 mlminmmHg; P < 0.05), but the total change in LVC during exercise was unaffected because of a significant reduction in the amplitude of the rapid decay phase and tendency ( P = 0.1) for a lower amplitude of the slow decay phase. Conclusion: Increased sympathetic constraint of vasodilation persists during initial contractions but is overcome at the high intensity by a mechanism apparently related to hyperaemic decay. [ABSTRACT FROM AUTHOR]