Endothelium-dependent relaxation by uridine tri- and diphosphate in isolated human pial vessels

Uridine triphosphate (UTP) and uridine diphosphate (UDP) are present in platelets, probably linked to storage organelles. In several animal species, UTP is a powerful constrictor of cerebral arteries, with no detectable dilatory component, which was confirmed in the present study. When testing the vasomotor effects of UTP and UDP in precontracted isolated segments of human pial arteries it was found that these nucleotides were powerful, transient dilators in the concentration range 10(-7)-10(-5) M in the majority of vessels studied. At higher doses a contractile response supervened. Uridine monophosphate and uridine were without effect. Removal of the vessel endothelium mechanically or by perfusion with Triton abolished the dilatory response, and now the contraction appeared already at 3 X 10(-6) M. The present findings add UTP and UDP among the group of endothelium-linked biogenic vasodilators. This may be of pathophysiological importance in the maintenance of an adequate brain circulation in disorders involving platelet dysfunction.