Differential localization of P2 receptor subtypes in mesenteric arteries and veins of normotensive and hypertensive rats

ATP acts at P2 receptors to contract blood vessels and reactivity to vasoconstrictor agents is often altered in hypertension. This study was designed to identify P2 receptors in mesenteric arteries and veins and to determine whether ATP reactivity is altered in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Computer-assisted video microscopy was used to measure vessel diameter in vitro. ATP was a more potent constrictor of veins (EC(50) = 2.7 microM) than arteries (EC(50) = 196 microM) from normotensive rats; there was no change in ATP reactivity in vessels from DOCA-salt rats. The P2X1 receptor agonist alpha,beta-methylene ATP (alpha,beta-MeATP, 0.03-3 microM) contracted arteries but not veins. ATP-induced contractions in arteries were blocked by alpha,beta-MeATP (3 microM) desensitization. 2-Methylthio-ATP (0.1-10 microM), an agonist that can act at P2Y1 receptors, did not contract arteries or veins, whereas UTP, an agonist at rat P2Y2/P2Y4 receptors, contracted veins (EC(50) = 15 microM) and arteries (EC(50) = 24 microM). UTP-induced contractions of veins cross-desensitized with ATP, whereas UTP-induced contractions in arteries were unaffected by alpha,beta-MeATP-desensitization. The P2X/P2Y1 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4-disulfonic acid blocked ATP-induced contractions of arteries (IC(50) = 4.8 microM) but not veins. Suramin, an antagonist that blocks P2Y2 receptors, partly inhibited ATP- and UTP-induced contractions of veins. Immunohistochemical studies revealed P2X1 receptor immunoreactivity in arteries but not veins. These data indicate that mesenteric vascular reactivity to ATP is not altered in DOCA-salt hypertension. ATP acts at P2X1 and P2Y2 receptors to contract mesenteric arteries and veins, respectively, whereas in arteries UTP acts at an unidentified P2 receptor.