Uridine adenosine tetraphosphate (Up4A) was reported as a novel endothelium-derived contracting factor. Up4A contains both purine and pyrimidine moieties, which activate purinergic (P2)X and P2Y receptors. However, alterations in the vasoconstrictor responses to Up 4A in hypertensive states remain unclear. The present study examined the effects of Up 4A on contraction of isolated renal arteries (RA) and pulmonary arteries (PA) from DOCA-salt rats using isometric tension recording. RA from DOCAsalt rats exhibited increased contraction to Up 4A versus arteries from control uninephrectomized rats in the absence and presence of N Gnitro- L-arginine (nitric oxide synthase inhibitor). On the other hand, the Up 4A-induced contraction in PA was similar between the two groups. Up 4A-induced contraction was inhibited by suramin (nonselective P2 antagonist) but not by diinosine pentaphosphate pentasodium salt hydrate (Ip 5I; P2X 1 antagonist) in RA from both groups. Furthermore, 2-thiouridine 5′-triphosphate tetrasodium salt (2-Thio- UTP; P2Y 2 agonist)-, uridine-5′-(γ-thio)-triphosphate trisodium salt (UTPγS; P2Y 2/P2Y 4 agonist)-, and 5-iodouridine-5′-O-diphosphate trisodium salt (MRS 2693; P2Y 6 agonist)-induced contractions were all increased in RA from DOCA-salt rats. Protein expression of P2Y 2-, P2Y 4-, and P2Y 6 receptors in RA was similar between the two groups. In DOCA-salt RA, the enhanced Up 4A-induced contraction was reduced by PD98059, an ERK pathway inhibitor, and Up 4Astimulated ERK activation was increased. These data are the first to indicate that Up 4A-induced contraction is enhanced in RA from DOCA-salt rats. Enhanced P2Y receptor signaling and activation of the ERK pathway together represent a likely mechanism mediating the enhanced Up 4A-induced contraction. Up 4A might be of relevance in the pathophysiology of vascular tone regulation and renal dysfunction in arterial hypertension.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Aug 2011|
- Extracellular nucleotide
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)