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Role of adenosine and nitric oxide in hypoxia‐induced skeletal muscle vasodilation in humans
Author(s) -
Leuenberger Urs A.,
Mascarenhas Ver,
LnintonFrazier Latoya,
Steiner Jill,
Hogeman Cynthia,
Gray Kristen S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1173.14
Subject(s) - aminophylline , vasodilation , adenosine , hypoxia (environmental) , adenosine receptor , omega n methylarginine , medicine , endocrinology , nitric oxide , skeletal muscle , nitric oxide synthase , brachial artery , forearm , anesthesia , pharmacology , chemistry , receptor , anatomy , blood pressure , organic chemistry , oxygen , agonist
In humans, systemic hypoxia evokes vasodilation in resting skeletal muscle despite significant increases in sympathetic vasoconstrictor nerve activity. This is thought to be due to endogenous vasodilators such as adenosine and nitric oxide (NO). To test whether adenosine and NO act independently, we determined the forearm blood flow responses to systemic hypoxia (FiO 2 0.1 for 10 min) during 1) inhibition of adenosine receptors (aminophylline), 2) inhibition of NO‐synthase (NG‐monomethyl‐L‐arginine, L‐NMMA), and 3) combined inhibition of adenosine receptors and NO‐synthase (aminophylline plus L‐NMMA) administered via brachial artery in healthy humans. Forearm blood flow (FBF, venous plethysmography) was compared in the infused (experimental) and opposite (control) forearms. During hypoxia (pO 2 35±1 mmHg), FBF in the control forearm increased by ~50%. L‐NMMA alone (n=8) reduced hypoxia‐induced vasodilation by ~37% whereas aminophylline alone (n=9) reduced it by ~50%. Combined blockade with aminophylline plus L‐NMMA (n=8) did not inhibit hypoxia‐induced vasodilation more greatly than either agent alone. These data demonstrate that both adenosine and NO contribute to hypoxia‐induced skeletal muscle vasodilation. The lack of synergy between aminophylline and L‐NMMA suggests that adenosine and NO may be part of the same vasodilator signaling cascade. (Supported by P01 HL077670 and R01 HL068699)