TY - JOUR
T1 - Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients
AU - Iepsen, Ulrik Winning
AU - Munch, Gregers Druedal Wibe
AU - Ryrsø, Camilla Koch
AU - Secher, Niels H.
AU - Lange, Peter
AU - Thaning, Pia
AU - Pedersen, Bente Klarlund
AU - Mortensen, Stefan P.
PY - 2018/2
Y1 - 2018/2
N2 - 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 sympatho-lysis) 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.
AB - 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 sympatho-lysis) 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.
KW - Exercise
KW - Functional sympatholysis
KW - Leg blood flow
KW - Humans
KW - Middle Aged
KW - Femoral Artery/drug effects
KW - Male
KW - Quadriceps Muscle/blood supply
KW - Lower Extremity/blood supply
KW - Regional Blood Flow
KW - Signal Transduction/drug effects
KW - Tyramine/administration & dosage
KW - Case-Control Studies
KW - Vasodilation/drug effects
KW - Pulmonary Disease, Chronic Obstructive/diagnosis
KW - Sympathomimetics/administration & dosage
KW - Female
KW - Aged
KW - Receptors, Adrenergic, alpha/metabolism
KW - Adenosine Triphosphate/administration & dosage
KW - Vasoconstriction/drug effects
KW - Vasodilator Agents/administration & dosage
KW - Infusions, Intra-Arterial
U2 - 10.1152/ajpheart.00398.2017
DO - 10.1152/ajpheart.00398.2017
M3 - Journal article
C2 - 29030339
SN - 0363-6135
VL - 314
SP - H180-H187
JO - American Journal of Physiology: Heart and Circulatory Physiology
JF - American Journal of Physiology: Heart and Circulatory Physiology
IS - 2
ER -