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 μg dl−1 min−1, n=10), the blocker of Na+/K+-ATPase ouabain (0.2 μg dl−1 min−1, n=8), the blocker of KCa channels tetraethylammonium chloride (TEA, 0.1 μg dl−1 min−1, n=10), nor by the KATP-channel blocker glibenclamide (2 μg 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