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 vasoco nstrictor 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)-sal t hypertensive rats. Computer-assisted video microscopy was used to measure vessel diameter in vitro. ATP was a more potent constrictor of veins (EC50 = 2.7 muM) than arteries (EC50 = 196 mM) from normotensive rats; there was no change in ATP reactivity in vessels from DOCA-salt rats. The P2X(1) rec eptor agonist alpha,beta -methylene ATP (alpha,beta -MeATP, 0.03-3 muM) con tracted arteries but not veins. ATP-induced contractions in arteries were b locked by alpha,beta -MeATP (3 muM) desensitization. 2-Methylthio-ATP (0.1- 10 muM), an agonist that can act at P2Y(1) receptors, did not contract arte ries or veins, whereas UTP, an agonist at rat P2Y(2)/P2Y(4) receptors, cont racted veins (EC50 = 15 muM) and arteries (EC50 = 24 muM). UTP-induced cont ractions of veins cross-desensitized with ATP, whereas UTP-induced contract ions in arteries were unaffected by alpha,beta -MeATP-desensitization. The P2X/P2Y(1) receptor antagonist pyridoxal-phosphate- 6-azophenyl-2',4-disulf onic acid blocked ATP-induced contractions of arteries (IC50 = 4.8 muM) but not veins. Suramin, an antagonist that blocks P2Y(2) receptors, partly inh ibited ATP- and UTP-induced contractions of veins. Immunohistochemical stud ies revealed P2X(1) receptor immunoreactivity in arteries but not veins. Th ese data indicate that mesenteric vascular reactivity to ATP is not altered in DOCA-salt hypertension. ATP acts at P2X(1) and P2Y(2) receptors to cont ract mesenteric arteries and veins, respectively, whereas in arteries UTP a cts at an unidentified P2 receptor.