Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition.
The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake, specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed three 5-min bouts of light knee-extensor exercise. Skeletal muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA), and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L-NMMA and indomethacin. At rest, inhibition of NOS alone and in combination with indomethacin reduced (P < 0.05) muscle blood flow. NOS inhibition increased (P < 0.05) limb oxygen extraction fraction (OEF) more than the reduction in muscle blood flow, resulting in an ∼20% increase (P < 0.05) in resting muscle oxygen consumption. During exercise, muscle blood flow and oxygen uptake were not altered with NOS inhibition, whereas muscle OEF was increased (P < 0.05). NOS and COX inhibition reduced (P < 0.05) blood flow in working quadriceps femoris muscle by 13%, whereas muscle OEF and oxygen uptake were enhanced by 51 and 30%, respectively. In conclusion, by specifically measuring blood flow and oxygen uptake by the use of PET instead of whole limb measurements, the present study shows for the first time in humans that inhibition of NO formation enhances resting muscle oxygen uptake and that combined inhibition of NOS and COX during exercise increases muscle oxygen uptake.
Turku PET Centre, Turku, Finland. ilkka.heinonen@tyks.fi
Ilkka
I
Heinonen
Heinonen
H
Ilkka
Bengt
B
Saltin
Saltin
S
Bengt
Jukka
J
Kemppainen
Kemppainen
K
Jukka
Hannu T
HT
Sipilä
Vesa
V
Oikonen
Oikonen
O
Vesa
Pirjo
P
Nuutila
Nuutila
N
Pirjo
Juhani
J
Knuuti
Knuuti
K
Juhani
Kari
K
Kalliokoski
Kalliokoski
K
Kari
Ylva
Y
Hellsten
Hellsten
H
Ylva
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007717:Knee / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012146:Rest / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; D007213:Indomethacin