Prostaglandin production contributes to exercise-induced vasodilation in heart failure.
Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 +/- 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1alpha was also measured. During control exercise, leg blood flow increased from 0.34 +/- 0.03 to 1. 99 +/- 0.19 l/min (P < 0.001), leg O2 consumption from 13.6 +/- 1.8 to 164.5 +/- 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 +/- 8.5 to 267.4 +/- 35.8 pg/min (P < 0.001). Indomethacin suppressed release of prostaglandin F1alpha (P < 0.001) throughout exercise and decreased leg blood flow during exercise (P < 0.05). This was associated with a corresponding decrease in leg O2 consumption (P < 0.05) and a higher level of femoral venous lactate at peak exercise (P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure.
Lang
C C
CC
Division of Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6300, USA.
Chomsky
D B
DB
Butler
J
J
Kapoor
S
S
Wilson
J R
JR
D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007866:Leg / Q000098:blood supply; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011460:Prostaglandins F; C100006:prostaglandin F1; D007213:Indomethacin