TY - JOUR

T1 - Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation

AU - Mortensen, Stefan

AU - Nyberg, Michael

AU - Thaning, Pia

AU - Saltin, Bengt

AU - Hellsten, Ylva

N1 - Keywords: Adenosine; Adult; Analysis of Variance; Cohort Studies; Exercise; Humans; Hyperemia; Indomethacin; Leg; Male; Muscle, Skeletal; Nitric Oxide; Prostaglandins; Receptors, Purinergic P1; Reference Values; Regional Blood Flow; Sensitivity and Specificity; Theophylline; Vasodilation; Young Adult; omega-N-Methylarginine

PY - 2009

Y1 - 2009

N2 - Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in synergy to regulate skeletal muscle hyperemia by determining the following: (1) the effect of adenosine receptor blockade on skeletal muscle exercise hyperemia with and without simultaneous inhibition of prostaglandins (indomethacin; 0.8 to 1.8 mg/min) and NO (N(G)-mono-methyl-l-arginine; 29 to 52 mg/min); (2) whether adenosine-induced vasodilation is mediated via formation of prostaglandins and/or NO; and (3) the femoral arterial and venous plasma adenosine concentrations during leg exercise with the microdialysis technique in a total of 24 healthy, male subjects. Inhibition of adenosine receptors (theophylline; 399+/-9 mg, mean +/- SEM) or combined inhibition of prostaglandins and NO formation inhibited the exercise-induced increase in leg blood flow by 14+/-1% and 29+/-2% (P<0.05), respectively, but combined inhibition of prostaglandins, NO, and adenosine receptors did not result in an additive reduction of leg blood flow (31+/-5%). Femoral arterial infusion of adenosine increased leg blood flow from approximately 0.3 to approximately 2.5 L/min. Inhibition of prostaglandins or NO, or prostaglandins and NO combined, inhibited the adenosine-induced increase in leg blood flow by 51+/-3%, 39+/-8%, and 66+/-8%, respectively (P<0.05). Arterial and venous plasma adenosine concentrations were similar at rest and during exercise. These results suggest that adenosine contributes to the regulation of skeletal muscle blood flow by stimulating prostaglandin and NO synthesis.

AB - Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in synergy to regulate skeletal muscle hyperemia by determining the following: (1) the effect of adenosine receptor blockade on skeletal muscle exercise hyperemia with and without simultaneous inhibition of prostaglandins (indomethacin; 0.8 to 1.8 mg/min) and NO (N(G)-mono-methyl-l-arginine; 29 to 52 mg/min); (2) whether adenosine-induced vasodilation is mediated via formation of prostaglandins and/or NO; and (3) the femoral arterial and venous plasma adenosine concentrations during leg exercise with the microdialysis technique in a total of 24 healthy, male subjects. Inhibition of adenosine receptors (theophylline; 399+/-9 mg, mean +/- SEM) or combined inhibition of prostaglandins and NO formation inhibited the exercise-induced increase in leg blood flow by 14+/-1% and 29+/-2% (P<0.05), respectively, but combined inhibition of prostaglandins, NO, and adenosine receptors did not result in an additive reduction of leg blood flow (31+/-5%). Femoral arterial infusion of adenosine increased leg blood flow from approximately 0.3 to approximately 2.5 L/min. Inhibition of prostaglandins or NO, or prostaglandins and NO combined, inhibited the adenosine-induced increase in leg blood flow by 51+/-3%, 39+/-8%, and 66+/-8%, respectively (P<0.05). Arterial and venous plasma adenosine concentrations were similar at rest and during exercise. These results suggest that adenosine contributes to the regulation of skeletal muscle blood flow by stimulating prostaglandin and NO synthesis.

U2 - 10.1161/HYPERTENSIONAHA.109.130880

DO - 10.1161/HYPERTENSIONAHA.109.130880

M3 - Journal article

C2 - 19433775

VL - 53

SP - 993

EP - 999

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 6

ER -