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Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb
Author(s) -
Ray Clare J.,
Marshall Janice M.
Publication year - 2009
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.2008.163691
Subject(s) - hyperaemia , adenosine , vasodilation , medicine , isometric exercise , endocrinology , skeletal muscle , chemistry , nitric oxide , muscle contraction , hindlimb , adenosine receptor , exertion , receptor , agonist , blood flow
Exercise hyperaemia is partly mediated by adenosine A 2A ‐receptors. Adenosine can evoke nitric oxide (NO) release via endothelial A 2A ‐receptors, but the role for NO in exercise hyperaemia is controversial. We have investigated the contribution of NO to hyperaemia evoked by isometric twitch contractions in its own right and in interaction with adenosine. In three groups of anaesthetized rats the effect of A 2A ‐receptor inhibition with ZM241385 on femoral vascular conductance (FVC) and hindlimb O 2 consumption at rest and during isometric twitch contractions (4 Hz) was tested (i) after NO synthase inhibition with l‐ NAME, and when FVC had been restored by infusion of (ii) an NO donor (SNAP) or (iii) cell‐permeant cGMP. Exercise hyperaemia was significantly reduced (32%) by l‐ NAME and further significantly attenuated by ZM241385 (60% from control). After restoring FVC with SNAP or 8‐bromo‐cGMP, l‐ NAME did not affect exercise hyperaemia, but ZM241385 still significantly reduced the hyperaemia by 25%. There was no evidence that NO limited muscle during contraction. These results indicate that NO is not required for adenosine release during contraction and that adenosine released during contraction does not depend on new synthesis of NO to produce vasodilatation. They also substantiate our general hypothesis that the mechanisms by which adenosine contributes to muscle vasodilatation during systemic hypoxia and exercise are different: we propose that, during muscle contraction, adenosine is released from skeletal muscle fibres independently of NO and acts directly on A 2A ‐receptors on the vascular smooth muscle to cause vasodilatation.