Uridine adenosine tetraphosphate induces contraction and relaxation in rat aorta

Uridine adenosine tetraphosphate (Up₄A) has been recently reported as an endothelium-derived vasoconstrictor and plasma levels of this dinucleotide are increased in juvenile hypertensive subjects. This study aimed to evaluate the vascular actions of Up₄A, typify the putative purinergic receptors that might mediate these effects and characterize the intracellular signaling pathways that may govern Up₄A responses. Up₄A induced a modest endothelium-dependent relaxation of rat aortic rings contracted with phenylephrine. From baseline, Up₄A induced concentration-dependent contractions that were significantly potentiated by endothelium removal or nitric oxide synthase inhibition. The contractile response induced by Up₄A was not tachyphylactic and was significantly reduced in the presence of P1 or P2X receptor antagonists, L-type Ca²⁺ channel blocker and Rho-kinase inhibitor. Up₄A-induced contraction apparently involves superoxide anion formation since it was significantly reduced by treatment with apocynin or tempol. This study presents the unique findings that the endogenous compound Up₄A is able to induce relaxation in addition to contraction of rat aorta. Up₄A-induced contraction is modulated by nitric oxide production, mediated by P1 and P2X receptor activation, and involves L-type Ca²⁺ channels, Rho-kinase pathway and superoxide formation.