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ATP‐induced vasodilation in human skeletal muscle
Author(s) -
Van Ginneken E E M,
Meijer P,
Verkaik N,
Smits P,
Rongen G A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705589
Subject(s) - glibenclamide , vasodilation , tetraethylammonium , sodium nitroprusside , tetraethylammonium chloride , medicine , chemistry , endocrinology , adenosine triphosphate , adenosine , forearm , ouabain , pharmacology , anesthesia , sodium , nitric oxide , anatomy , potassium , organic chemistry , diabetes mellitus
The purine nucleotide adenosine‐5′‐triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium‐derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. Adenosine 5′‐triphosphate (0.2, 0.6, 6 and 20 nmol dl −1 forearm volume min −1 ) evoked a dose‐dependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 μ g dl −1 min −1 , n =10), the blocker of Na + /K + ‐ATPase ouabain (0.2 μ g dl −1 min −1 , n =8), the blocker of K Ca channels tetraethylammonium chloride (TEA, 0.1 μ g dl −1 min −1 , n =10), nor by the K ATP ‐channel blocker glibenclamide (2 μ g dl −1 min −1 , n =10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and L ‐NMMA ( n =6) significantly increased the baseline forearm vascular resistance. The ATP‐induced relative decreases in forearm vascular resistance were 48±5, 67±3, 88±2, and 92±2% in the absence and 23±7, 62±4, 89±2, and 93±1% in the presence of the combination of TEA, indomethacin and L ‐NMMA ( P <0.05, repeated‐measures ANOVA, n =6). A similar inhibition was obtained for sodium nitroprusside (SNP, P <0.05 repeated‐measures ANOVA, n =6), indicating a nonspecific interaction due to the blocker‐induced vasoconstriction. ATP‐induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and L ‐NMMA. Endothelium‐independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies.British Journal of Pharmacology (2004) 141 , 842–850. doi: 10.1038/sj.bjp.0705589