Extracellular nucleotides ATP and UTP induce a marked acute release of tissue-type plasminogen activator in vivo in man

Extracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tP4 release from the vascu lar endothelium in vivo. Nine healthy subjects were studied in a perfused-f orearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by ind omethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p le ss than or equal to0.01 for both) in conjunction with pronounced vasodilati on. Neither the acute tPA release nor the vasodilation could be abrogated b y NO and prostanoid synthesis inhibition. The similar effect of ATP and UTP suggests that P2Y rather than adenosine receptors mediate the response. Re lease of extracellular nucleotides in ischemic tissue may induce a pronounc ed activation of the endogenous fibrinolytic system.