Nitric oxide contributes to the augmented vasodilatation during hypoxic exercise

Darren P. Casey, Brandon D. Madery, Timothy B. Curry, John H. Eisenach, Brad W. Wilkins, Michael J. Joyner

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


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 O2 saturation). In protocol 1 (n= 12), subjects received intra-arterial administration of saline (control) and the NO synthase inhibitor NG-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 (Δ 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 ΔFVC due to hypoxic exercise compared to saline (control; P < 0.01). However, the relative reduction in ΔFVC 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.

Original languageEnglish (US)
Pages (from-to)373-385
Number of pages13
JournalJournal of Physiology
Issue number2
StatePublished - Jan 2010

ASJC Scopus subject areas

  • Physiology


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