Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate (Up4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y2/P2Y4 agonist), UDP (P2Y6 agonist), and α,β-methylene ATP (P2X1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X1, but not P2Y2 or P2Y6 was decreased; (3) in small mesenteric artery, Up4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y2 and P2X1 was decreased whereas P2Y6 expression was increased; (4) in femoral artery, Up4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y2, P2Y6 and P2X1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up4A may be adaptive to the vascular alterations produced by hypertension.

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