Vol. 296, Issue 2, 478-485, February 2001

Differential Localization of P2 Receptor Subtypes in Mesenteric Arteries and Veins of Normotensive and Hypertensive Rats

James J. Galligan, Margaret C. Hess, Sara B. Miller and Gregory D. Fink

Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan

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 (EC₅₀ = 2.7 µM) than arteries (EC₅₀ = 196 µM) from normotensive rats; there was no change in ATP reactivity in vessels from DOCA-salt rats. The P2X₁ receptor agonist ,-methylene ATP (,-MeATP, 0.03-3 µM) contracted arteries but not veins. ATP-induced contractions in arteries were blocked by ,-MeATP (3 µM) desensitization. 2-Methylthio-ATP (0.1-10 µM), 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 (EC₅₀ = 15 µM) and arteries (EC₅₀ = 24 µM). UTP-induced contractions of veins cross-desensitized with ATP, whereas UTP-induced contractions in arteries were unaffected by ,-MeATP-desensitization. The P2X/P2Y₁ receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4-disulfonic acid blocked ATP-induced contractions of arteries (IC₅₀ = 4.8 µM) 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.