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Measurement of nitric oxide release evoked by systemic hypoxia and adenosine from rat skeletal muscle in vivo
Author(s) -
Ray Clare J.,
Marshall Janice M.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.094854
Subject(s) - adenosine , hypoxia (environmental) , endocrinology , medicine , vasodilation , adenosine a1 receptor , adenosine receptor , nitric oxide , nitroarginine , chemistry , nitric oxide synthase , anesthesia , receptor , oxygen , agonist , organic chemistry
It is accepted that NO plays a role in hypoxic vasodilatation in several tissues. For rat hindlimb muscle there is evidence that during systemic hypoxia endogenously released adenosine acts on endothelial A 1 receptors to evoke dilatation in a NO‐dependent fashion, implying requirement for, or mediation by, NO. We tested in vivo whether systemic hypoxia and adenosine release NO from muscle. In anaesthetized rats, arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded allowing computation of femoral vascular conductance (FVC). Blood samples taken from femoral artery and vein allowed electrochemical measurement of plasma [NO] after reduction of NO 3 − and NO 2 − . Systemic hypoxia and adenosine infusion for 5 min each, evoked an increase in FVC that was attenuated by the NO synthase (NOS) inhibitor l ‐NAME (Group 1, n = 8) and adenosine A 1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, Group 2, n = 6). Concomitant systemic hypoxia and adenosine infusion evoked increases in venous–arterial [NO] difference ([NO] v‐a ) from −1.4 ± 0.85 to 6.6 ± 1.6 and 2.3 ± 0.78 to 8.4 ± 1.8 nmol l −1 , respectively (mean ± s.e.m ), which were abolished by l ‐NAME (−0.72 ± 0.90 to −0.87 ± 0.74 and 0.72 ± 0.85 to −0.97 ± 1.1 nmol l −1 , respectively). DPCPX also abolished the hypoxia‐evoked increase in [NO] v‐a (control −4.2 ± 1.8 to 12.5 ± 3.7 nmol l −1 , with DPCPX −0.63 ± 2.6 to 3.3 ± 2.9 nmol l −1 ) and decreased the adenosine‐evoked increase in [NO] v‐a (control 1.1 ± 1.5 to 24 ± 14, with DPCPX −0.43 ± 2.9 to 12 ± 5.9 nmol l −1 ). These results allow the novel conclusion that the muscle vasodilatation of systemic hypoxia is partly mediated by adenosine acting at endothelial A 1 receptors to stimulate synthesis and release of NO, which then induces dilatation.