Nitric oxide contributes to the augmented vasodilatation during hypoxic exercise.
We tested the hypotheses that (1) nitric oxide (NO) contributes to augmented skeletal muscle vasodilatation during hypoxic exercise and (2) the combined inhibition of NO production and adenosine receptor activation would attenuate the augmented vasodilatation during hypoxic exercise more than NO inhibition alone. In separate protocols subjects performed forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O(2) saturation). In protocol 1 (n = 12), subjects received intra-arterial administration of saline (control) and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). In protocol 2 (n = 10), subjects received intra-arterial saline (control) and combined L-NMMA-aminophylline (adenosine receptor antagonist) administration. Forearm vascular conductance (FVC; ml min(-1) (100 mmHg)(-1)) was calculated from forearm blood flow (ml min(-1)) and blood pressure (mmHg). In protocol 1, the change in FVC (Delta from normoxic baseline) due to hypoxia under resting conditions and during hypoxic exercise was substantially lower with L-NMMA administration compared to saline (control; P < 0.01). In protocol 2, administration of combined L-NMMA-aminophylline reduced the DeltaFVC due to hypoxic exercise compared to saline (control; P < 0.01). However, the relative reduction in DeltaFVC compared to the respective control (saline) conditions was similar between L-NMMA only (protocol 1) and combined L-NMMA-aminophylline (protocol 2) at 10% (-17.5 +/- 3.7 vs. -21.4 +/- 5.2%; P = 0.28) and 20% (-13.4 +/- 3.5 vs. -18.8 +/- 4.5%; P = 0.18) hypoxic exercise. These findings suggest that NO contributes to the augmented vasodilatation observed during hypoxic exercise independent of adenosine.
Casey
Darren P
DP
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA. casey.darren@mayo.edu
Madery
Brandon D
BD
Curry
Timothy B
TB
Eisenach
John H
JH
Wilkins
Brad W
BW
Joyner
Michael J
MJ
D000328:Adult; D000628:Aminophylline / Q000494:pharmacology; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D000628:Aminophylline; D009569:Nitric Oxide